texas implementation of medication algorithms (tima...

9/28/99

TEXAS IMPLEMENTATION OF MEDICATION ALGORITHMS(TIMA)

Guidelines for Treating Major Depressive Disorder

TIMA PHYSICIANPROCEDURAL MANUAL

Madhukar H. Trivedi, M.D.

Steven Shon, M.D.

M. Lynn Crismon, Pharm. D.

Tracie Key, R.N., B.S.N.

Revised 9/2000

(Last edited 12/00)

Address Correspondence to:

Madhukar Trivedi, M.D.Associate ProfessorDirector, Depression Module Texas Medication Algorithm ProjectDirector, Depression and Anxiety Disorders ProgramUniversity of Texas Southwestern Medical School at DallasSt. Paul POB I, Suite #6005959 Harry Hines BoulevardDallas, Texas 75235-9101

Phone: (214) 648-4282Fax: (214) 648-4210E-mail: [email protected]

TIMA MDD Physician's Manual Page i 9/28/99

Table of Contents Depression Algorithms Manual

Page

♦ Overview of TIMA 1

♦ Administrative Structure 4

♦ Depression AlgorithmsNonpsychotic Depression Algorithm Flowchart 5Psychotic Depression Algorithm Flowchart 6Critical Decision Point Flowchart 7

♦ Algorithms at a Glance 8

Algorithm Strategies 9Critical Decision Points and Algorithm Tactics 10Antidepressant Dosing 11Side Effects for Antidepressant Medications 12Antipsychotic Dosing 13Side Effects for Antipsychotic Medications 13Augmentation Dosing 14Side Effects for Augmentation Agents 14Associated Symptoms Treatments 15Treatment Emergent Side Effect Treatments 15Switching Medications 16Combining Antidepressants 18

♦ Algorithm Implementation 19

♦ Critical Decision Points for the Nonpsychotic Depression Algorithm 22

♦ Critical Decision Points for the Psychotic Depression Algorithm 35

♦ Continuation and Maintenance Phase TreatmentContinuation Phase Treatment 45Maintenance Phase Treatment 46

TIMA MDD Physician's Manual Page ii 9/28/99

♦ Appendix

DSM-IV Criteria for Major Depressive DisorderMedication Information

Antidepressant MedicationsAugmentation AgentsAntipsychotic MedicationsSwitching Between Antidepressant Medications

Process MeasuresInventory of Depressive Symptoms Self-Report (IDS-SR)Scoring Criteria for IDS-SRScoring Criteria for Physician- and Patient-Rated Overall Symptom

and Side Effect RatingsDocumentation

Instructions for Outpatient Data CollectionOutpatient Intake FormOutpatient Clinic Visit Clinical Record FormOutpatient Interim Contact Form

Forms for Outpatient Data CollectionOutpatient Intake FormOutpatient Clinic Visit Clinical Record FormOutpatient Interim Contact Form

Instructions for Inpatient Data CollectionInpatient Intake Form/Annual UpdateInpatient Clinical Record FormInpatient Contact Form

Forms for Inpatient Data CollectionInpatient Intake Form/Annual UpdateInpatient Clinical Record FormInpatient Contact Form

CommunicationsImportant Telephone NumbersConference Call Schedule

Question and Response Fax Form

TIMA MDD Physician's Manual Page iii 9/28/99

These guidelines reflect the state of knowledge, current at the time of publication, on effectiveand appropriate care, as well as clinical consensus judgements when knowledge is lacking.The inevitable changes in the state of scientific information and technology, mandate thatperiodic review, updating, and revisions will be needed. These guidelines (algorithms) do notapply to all patients, and each must be adapted and tailored to each individual patient. Properuse, adaptation modifications or decisions to disregard these or other guidelines, in whole or inpart, are entirely the responsibility of the clinician who uses the guidelines.

The documents in the TIMA web site are in the public domain and may be used and reprintedwithout special permission, except for those copy righted materials noted for which furtherreproduction is prohibited without the specific permission of the copyright holders. Propercitation is appreciated by the authors. The authors bear no responsibility for the use of theseguidelines by third parties.

TIMA

TIMA MDD Physician's Manual Page 1 9/28/99

Overview of TIMA Algorithms facilitate clinical decision making by providing physicians with large amounts ofcurrent information on the newest psychotropic medications and research data, as well asspecific treatment sequences with tactical recommendations. Patients receive the benefit ofpatient education, which should enhance adherence to the treatment program. Algorithms aredesigned with the objectives of long-term safety, tolerability, and full symptom remission — notjust response. The employment of such treatment guidelines to aggressively treat the severelyand persistently mentally ill (SPMI) population may bring about a decrease in the use ofcrisis/hospital services and the number of clinical visits — while presenting an accountabilityfor scarce resources — thereby increasing the overall efficiency of patient care.

Beginning in 1995, The Texas Medication Algorithm Project (TMAP) was developed by theTexas Department of Mental Health and Mental Retardation (TDMHMR) in collaboration withTexas universities to assess the value of algorithms — along with clinical support and apatient/family educational package — in the pharmacological management of mentally illpatients. The result has been a set of algorithms for the treatment of the three major disordersmost commonly encountered in the Texas public mental health system: schizophrenia (SCZ),bipolar disorder (BPD), and major depressive disorder (MDD). TDMHMR has defined a bestpractice treatment as a series of treatment steps which guides physicians in determiningmedication treatment plans, thereby generating the best outcome for each individualconsumer. Practitioners, patients, families, and administrators all contributed to the formulationand implementation of TMAP, ensuring an optimum level of efficacy and practicality. Phase 1of TMAP dealt with the development of these algorithms using expert consensus. In Phase 2,the feasibility of algorithm implementation in the TDMHMR system was evaluated. The goal ofPhase 3 was to evaluate the clinical and economic impact of medication treatment algorithmsfor MDD, SCZ, and BPD in comparison with treatment as usual (TAU).

Up until now, the effectiveness of these medication algorithms has only been put to use with alimited sample of patients. Implementation of the algorithms on a systemwide basis is the nextstep in offering a higher quality of care to the SPMI patient population in the public mentalhealth sector. Texas Implementation of Medication Algorithms (TIMA) is Phase 4 of TMAP: the"roll-out" of these depression algorithms to TDMHMR clinics throughout the state. The roll-outof TIMA has begun with the training of physicians and support personnel in algorithmimplementation. Revisions may be required in the structure and function of clinical staff toincrease patient education and adherence, to improve follow up, and to develop psychosocialsupports to improve symptom recognition, symptom control, and functional restoration.Continuous education, consultation, and collaboration are necessary for both clinicians andadministrators in making timely revisions in clinical procedures and budgetary allocations.From a clinical and administrative perspective, medication algorithms should demonstratevalidity with far-reaching and long-term applications.

Relevant Publications:

Altshuler KZ, Rush AJ. Computerized Texas Medication Algorithm Project undergoes testing.Outcomes & Accountability Alert, 4:1,10-11, 1999.

Altshuler KZ, Rush AJ. Computerizing the Texas Medication Algorithm Project. BehavioralHealthcare Tomorrow, 8:38,41,1999.

TIMA


Biggs MM, Shores-Wilson K, Rush AJ, Carmody TJ, Trivedi MH, Crismon ML, Toprac MG,Mason M. A comparison of alternative assessments of depressive symptom severity: A pilotstudy. Psychiatry Research 2000;96:269-279.

Chiles JA, Miller AL, Crismon ML, Rush AJ, Krasnoff AS, Shon SS. The Texas MedicationAlgorithm Project: Development and implementation of the schizophrenia algorithm.Psychiatric Services 1999;50:69-74.

Crismon ML, Trivedi MH, Pigott TA, Rush AJ, Hirshfeld RMA, Kahn DA, DeBattista C, NelsonJC, Nierenberg AA, Sackeim HA, Thase ME. The Texas Medication Algorithm Project: Reportof the Texas Consensus Conference Panel on Medication Treatment of Major DepressiveDisorder. Journal of Clinical Psychiatry, 60:142-156, 1999.

Dennehy EB, Suppes T. Medication Algorithms for Bipolar Disorder. Journal of PracticalPsychiatry and Behavioral Health, 5:142-152, 1999.

Gilbert DA, Atlshuler KZ, Rago WV, Shon SP, Crismon ML, Toprac MG, Rush AJ. TexasMedication Algorithm Project: Definitions, rationale, and methods to develop medicationalgorithms. Journal of Clinical Psychiatry, 59:345-351, 1998.

Kashner TM, Rush AJ, Altshuler KZ. Measuring Costs of Guideline-Driven Mental Health Care:The Texas Medication Algorithm Project. Submitted.

Miller AL, Chiles JA, Chiles JK, Crismon ML, Rush AJ, Shon SP. The TMAP schizophreniaalgorithms. Journal of Clinical Psychiatry 1999;60:649-657.

Rush AJ, Crismon ML, Toprac MG, Shon SS, Rago WV, Miller AL, Suppes T, Trivedi MH,Biggs MM, Shores-Wilson K, Kashner TM, Altshuler KZ. Implementing Guidelines andSystems of Care: Experiences with the Texas Medication Algorithm Project (TMAP). Journal ofPractical Psychiatry and Behavioral Health, 5:75-86, 1999.

Rush AJ, Crismon ML, Toprac MG, Trivedi MH, Rago WV, Shon SP, Altshuler KZ. Consensusguidelines in the treatment of major depressive disorder. Journal of Clinical Psychiatry, 59(suppl 20):73-84, 1998.

Rush AJ, Rago WV, Crismon ML, Toprac MG, Shon P, Suppes T, Miller AL, Trivedi MH,Swann AC, Biggs MM, Shores-Wilson K, Kashner TM, Pigott T, Chiles JA, Gilbert DA,Altshuler KZ. Medication treatment of the severely and persistently mentally ill: The TexasMedication Algorithm Project. Journal of Clinical Psychiatry, 60:284-291, 1999.

Shon SP, Crismon ML, Toprac MG, Trivedi MH, Miller AL, Suppes T, Rush AJ. Mental healthcare from the public perspective: The Texas Medication Algorithm Project. Journal of ClinicalPsychiatry, 60 (suppl. 3):16-20, 1999.

Shon SP, Toprac MG, Crismon ML, Rush AJ. Strategies for implementing psychiatricmedication algorithms in the public sector. Journal of Practical Psychiatry and BehavioralHealth; 5:32-36, 1999.

Shon, SP. Mapping the Meds. Behavioral Health Management, 18:20-24, 1998.

TIMA


Shon, SP. Will TMAP make a difference? The Texas Medication Algorithm Project. TheJournal of the California Alliance for the Mentally Ill, 9:38-40, 1998.

Starkweather K, Shon SP, Crismon ML. A Texas-sized prescription: providers report progresswith medication guidelines. Behavioral Healthcare Tomorrow 2000;9(4):44-46.

Toprac MG, Rush AJ, Conner TM, Crismon ML, Dees M, Hopkins C, Rowe V, Shon SP. TheTexas Medication Algorithm Project patient and family education program: a consumer-guidedinitiiative. J Clin Psychiatry 2000;61:477-486.

Trivedi MH, DeBattista C, Fawcett J, Nelson C, Osser D, Stein D, Jobson K. Developingtreatment algorithms for unipolar depression in cyberspace: International PsychopharmacologyAlgorithm Project (IPAP). Psychopharmacolpgy Bulletin, 34(3):355-359, 1998.

Trivedi MH, Rush AJ, Crismon ML, O'Neal B, Toprac M. Treatment guidelines and algorithms.In: Dunner DL, Rosenbaum JF (eds.). Psychiatric Clinics of North America Annual Review ofDrug Therapy 2000. Philadelphia, PA: W.B. Saunders Co., 2000:1-22.

Acknowledgments

We wish to acknowledge the contribution of the TMAP project, which was supported by theRobert Wood Johnson Foundation, Meadows Foundation, Moody Foundation, Nannie HoganBoyd Charitable Trust, Texas Department of Mental Health and Mental Retardation, Center forMental Health Services, as well as Mental Health Connections, a partnership between DallasCounty Mental Health and Mental Retardation and the Department of Psychiatry, University ofTexas Southwestern Medical Center, which receives funding from the Texas State Legislatureand the Dallas County Hospital District. In addition, unrestricted educational grants wereprovided by Abbott Laboratories, Bristol-Myers Squibb Company, Eli Lilly and Company,Forest Laboratories, Glaxo-Wellcome, Inc., Janssen Pharmaceutica, Novartis PharmaceuticalsCorporation, Pfizer, Inc., U.S. Pharmacopeia and Wyeth-Ayerst Laboratories. The authorsappreciate the administrative support of Kenneth Z. Altshuler, M.D., Professor and Chairman,Department of Psychiatry, UT Southwestern Medical Center, Dallas, Texas, and of A. JohnRush, M.D., Professor and Vice Chairman for Research, Department of Psychiatry, UTSouthwestern Medical Center, Dallas, Texas. The authors also wish to thank Fast Word, Inc.,Dallas, for their technical support.

TIMA


Administrative Structure

Project Management Team

Steven Shon, M.D.

Madhukar Trivedi, M.D.

M. Lynn Crismon, Pharm.D.

Tawny Bettinger, Pharm.D.

Marcia Toprac, Ph.D.

Madhukar Trivedi, M.D.Project Director

M. Lynn Crismon, Pharm.D.Associate Director

Tawny Bettinger, Pharm.D.Clinical Pharmacologist

Steven Shon, M.D.Executive Advisor

Tracie Key, R.N., B.S.N.Project Coordinator


Depression Algorithms

Stage 3A

Strategies for the Treatment of Major Depression

(Nonpsychotic)Version 3

MonotherapySSRI‡, BUPSR, NEF, VLFXR or

MRT

Continuation

Stage 1

MonotherapySSRI‡, BUPSR, NEF, TCA,

VLFXR or MRTStage 2

MonotherapySSRI‡, BUPSR, NEF, TCA, VLFXR,

MRT, MAOI*From a class other than used in Stage 1 or 2

Stage 3

ECT

Stage 4

Response

Lithium Augmentation ***

ContinuationPartial Responseor Nonresponse

Response

Combination antidepressants:· TCA + SSRI� · BUPSR + SSRI‡ · NEF + SSRI‡ · BUPSR + NEF

Stage 5

Continuation

Stage 6

Any stage(s) can be skipped depending on the clinical picture.

Stage 1AAugmentation**

Partial Response or Nonresponse

Continuation

Response

Stage 2AAugmentation**Partial Response

or Nonresponse


Augmentation**Partial Response or Nonresponse



Continuation

Stage 7

Partial Responseor Nonresponse

Partial Responseor Nonresponse

OTHER e.g. Lamotrigine, Fluvoxamine,

MRT+BUP, Olanzapine, etc.(Provide Rationale)

* Consider TCA/VLF if not tried.** Lithium, thyroid, buspirone.*** Skip if Li augmentation has already failed.� Most studied combination‡ SSRI = Fluox, Sert, Parox, Cital

Response

Response

ContinuationResponse

Maintenance phase when

indicated

Partial Response Response

Partial Response Response

Partial Response

Depression ModuleTIMA


Strategies for the Treatment of Major Depression (Psychotic)

TCA + Typical AntipsychoticSSRI + Typical AntipsychoticVLF + Typical AntipsychoticTCA + Olanzapine/RisperidoneSSRI + Olanzapine/RisperidoneVLF + Olanzapine/RisperidoneAmoxapine

ContinuationStage 1

Efficacy Failure:1) If nonTCA, go to TCA2) If TCA, go to nonTCA or to Stage 3

Side Effect Failure: Different Drug

ContinuationStage 2

Nonresponse/ Partial response

ECT Continuation

Response

Stage 3

Previously Untried#1 Agent + LithiumAugmenting Agent

Continuation

Response

Stage 4

Nonresponse/Partial Response

Nonresponse/Partial response

Stage 5OTHER

Agent not used in Stages 1 or 2

Continuation

Nonresponse/Partial Response

Response

Response

Response

Go to Maintenance phase when

indicated


Critical Decision Points (CDPs) for Major Depressive Disorder

0%

Increase Dose

Go to Next Stage

Augment

Go to Next Stage

Increase Aug

Go to Next Stage

Go to Next Stage

%IMPROVEMENT

Continue

Increase Dose

Increase Dose

Continue

Augment

Go to Next Stage

Increase Aug

Augment

Go to Next Stage25%

50%

75%

100%

Go to Continuation Phase if >75% improvement is achieved,at 6 weeks.

Decision Point #1

Week 0

Decision Point #2

Week 4

Decision Point #3

Week 6

Decision Point #4

Week 8

Decision Point #5

Week 10

Decision Point #6

Week 12

or or or

or or

or

Continue

Continue

Increase Dose

Continue

Tactics for the Treatment of Major Depression (Nonpsychotic)

Continue

or ContinueContinue

Augment

Go to Next Stage

Increase Dose Augment

Go to Next Stage

or

or

or

or


Algorithms At A Glance

At-a-GlanceDepression Medication Algorithms

Visit Frequency: Weekly contact (office visit or by phone) for the first 4 weeks of eachstage; then every 2 weeks until 50% improvement in symptoms is maintained for atleast one month; then every 4 weeks until 75% improvement is maintained for at leastone month; then every 3 months. Support personnel may contact patients by phone ifthe physician is unable to see them.

Assessment Frequency: Inventory of Depressive Symptomatology - Self-Report(IDS-SR) and Clinical Report Form (CRF) at each clinic visit. If the patient is contactedby phone, an Interim Contact Form (ICF) must be completed.

Duration of Acute Treatment: Until 75% symptom improvement is achieved for 4weeks, then move to continuation phase. (See Critical Decision Points (CDP) Table 2,page 10.)

Response: Nonresponse (<25% improvement)Minimal response (25–50% improvement)Partial response (50–75% improvement)Full response/remission (75–100% improvement)

Criteria for Medication Change: Anything less than 75% improvement or fullresponse may require a medication change.

Evaluations: At each visit a physician assessment of core symptom severity, overallfunctional impairment, and side effect severity. Algorithm Coordinator (AC)assessments, using IDS-SR and patient global self-rating of symptom severity and sideeffects, should be done prior to patient contact with the physician.

Medication Switching: Discontinue or taper according to Table 11 on page 16 or theGuidelines for Switching Between Antidepressant Medications in the Appendix.

Medication Doses: See Tables 3, 5, and 7 on pages 11, 13, and 14 and theGuidelines in the Appendix for information on medications. Doses outside of theranges should have a chart note indicating “change from algorithmrecommended” and documentation of rationale for change.

Augmentation and Combination: If a partial response is achieved, physicians mayaugment with lithium, thyroid medication (Cytomel), or buspirone to potentiate a greaterresponse. A combination of 2 antidepressants, both at full doses, is suggested at Stage5 of the algorithm.


Table 1: Strategies for Acute Phase Treatment of Major Depressive Episodes

Stage Nonpsychotic Depression Psychotic Depression

Stage 1 Monotherapy1 Antidepressant + Antipsychotic♦ SSRI,2 Bupropion (BUP), Nefazodone

(NEF), Venlafaxine (VLF), Mirtazapine(MRT) (A evidence4)

♦ TCA + Antipsychotic (A-B evidence)4

♦ SSRI + Antipsychotic (B-C evidence)♦ Amoxapine (B evidence)♦ VLF + Antipsychotic (evidence)

Stage 2 Monotherapy Antidepressant + Antipsychotic♦ SSRI, BUP, NEF, VLF, Mirtazapine

(MRT) OR a TCA♦ EFFICACY FAILURE: Switch to

another antidepressant.♦ SIDE EFFECT FAILURE: Switch

classes, or consider staying within theclass if a contrasting SE profile isavailable or expected.

♦ EFFICACY FAILURE: If nonTCAused in Stage 1, switch to TCA. If TCAused, try an antidepressant from adifferent class.

♦ SIDE EFFECT FAILURE: Switch toan agent from a different class.

Stage 3 Monotherapy ECT♦ SSRI, BUP, NEF, VLF, MRT, TCA or

MAOI♦ Choose a medication from a different

class than used in Stage 1 or 2.

♦ If the patient refuses ECT or does notrespond, go to the next stage or repeat anearlier stage with a different agent.

Stage 4 Augmentation Augmentation♦ Previously untried antidepressant +

lithium, thyroid,5 or buspirone♦ Begin medications simultaneously.

♦ Previously untried treatment + lithium,thyroid,5 or buspirone

♦ Begin medications simultaneously.

Stage 5 Combination Therapy Other♦ TCA + SSRI, SSRI + BUP, SSRI +

NEF, BUPSR + NEF♦ Any antidepressant + antipsychotic not

tried in Stage 1 or 2

Stage 6 ECT Other♦ If patient refuses ECT or does not

respond, go to next stage or repeat anearlier stage with a different agent.

♦ Any antidepressant + antipsychotic nottried previously

Stage 7 Other Other♦ Any antidepressant or combination not

previously tried♦ Any antidepressant + antipsychotic not

tried previously

1 Acceptable antidepressants for Stage 1: Discuss treatment options with the patient and depending on prior treatment history, patient’s

clinical presentation, life style, and personal preferences, etc., assess the relative advantages of Stage 1 medications and make an initialtreatment selection.

2 FDA-approved SSRIs for depression include: fluoxetine (FLU), paroxetine (PRX), sertraline (SERT), and citalopram (CIT).

3 Acceptable TCAs for psychotic depression include: desipramine (DMI), nortriptyline (NT), amitriptyline (AMI), clomipramine (CMI),or imipramine (IMI).

4 Evidence level: A = controlled clinical trials; B = open trials and retrospective data analyses; C = clinical consensus and/or casereports.

5 T3 thyroid medication Cytomel (triiodothyronine) is suggested before T4 Synthroid.


Table 2: Critical Decision Points (CDPs) and Tacticsfor Acute Phase Treatment of Major Depression:

Within each strategy stage, approaches to conducting a therapeutic trial with an antidepressant

CriticalDecision Point Clinical Status Plan1

Week 0(CDP # 1)

Symptomatic ♦ Initiate medication; adjust dose to lower end of therapeuticdose range or serum level.

Week 4(CDP # 2)

Full Response ♦ Continue current dose.

Partial Response2 ♦ Continue current dose.♦ Consider increasing dose.

Minimal orNonresponse

♦ Increase dose.3

♦ Go to the next stage. Week 6(CDP # 3)

Full Response ♦ Go to continuation phase if full response sustained for at least4 weeks. Otherwise, continue current dose.

Partial Response ♦ Maximize dose.♦ Augment with lithium, thyroid, or buspirone.

Nonresponse orminimal response

♦ Augment with lithium or alternative augmenting agent.♦ Go to the next stage.

Week 8(CDP # 4)

Full Response ♦ Go to continuation phase if full response is sustained for atleast 4 weeks. Otherwise, continue current dose.

Partial Response ♦ Augment with lithium or alternative augmenting agent.♦ Go to the next stage.

Nonresponse orminimal responseto lithium oralternativeaugmentation for2–3 weeks

♦ Discontinue and go to the next stage.

Week 10(CDP # 5)


Partial Response ♦ Adjust dose (antidepressant and/or augmentation dose).♦ Go to the next stage.

Nonresponse orminimal response

♦ Go to the next stage.

Week 12(CDP # 6)


Partial Response ♦ Go to the next stage. 1 For patients showing minimal or no response, total trial should not exceed 4–8 weeks. For patients with a partial response the trial may

last up to 12 weeks to increase dose and implement augmentation strategy. Patients with only a partial response at any stage beyond 12weeks should be considered for a medication change or a move to a subsequent treatment stage. In cases of treatment resistantdepression (TRD), longer trials may be necessary in later stages.

2 With partial response, the clinician and patient assess both the absolute degree of improvement and the rate of improvement.Nonresponse is <25% improvement in overall symptoms, minimal response is 25–50% improvement in overall symptoms, partialresponse is 50–75% improvement in overall symptoms, full response is >75% improvement in overall symptoms.

3 In patients with psychotic depression, dose increases may include the antidepressant, the antipsychotic, and/or the augmenting agent.


Table 3: Antidepressant Dosing Used for Acute Phase Treatment of Depression

Type/ Class

Medication

Initial Target Dose

(Level)

Maximum Dose

(Level)

RecommendedAdministration

Schedule SSRI

Fluoxetine (Prozac) Paroxetine (Paxil) Sertraline (Zoloft) Citalopram (Celexa)

20 mg

20–30 mg 50–100 mg

20 mg

40–80 mg 40–60 mg

150–200 mg 60 mg

QAM QAM QAM QAM

TCA

Amitriptyline Clomipramine Desipramine Imipramine Nortriptyline

150–200 mg 100–150 mg

150 mg (>125ng/ml) 150 mg

(IMI+DMI>200 ng/ml) 75–100 mg

(50–150 ng/ml)

300 mg 250 mg 300 mg 300 mg

(200–400ng/ml) 150 mg

(50–150 ng/ml)

QHS QHS QHS QHS

QHS

Others

Amoxapine Bupropion SR (Wellbutrin SR) Bupropion (Wellbutrin) Mirtazapine (Remeron) Nefazodone (Serzone) Venlafaxine (Effexor) Venlafaxine XR

(Effexor XR)

200–300 mg 200–300 mg

225–300 mg

30 mg 200–400 mg 150–225 mg 75–225 mg

400 mg 400 mg

450 mg 60 mg 600 mg 375 mg 225 mg

QHS

bid<200mg/dose

tid<150mg/dose QHS bid bid QD

MAOIs

Phenelzine Tranylcypromine

45–60 mg 30–40 mg

90–120 mg 60–80 mg

QD–tid QD–tid

Also refer to the Antidepressant Monographs section in the Appendix.

Treatment of Depression with Antidepressants

• 50% of patients either do not receive adequate levels of antidepressants or are not treated for an adequate periodof time.

• 10–20% of patients are intolerant to an initial trial of antidepressant medication.

• 25–30% of patients who complete an adequate trial do not show an acceptable response.

• The strategies for achieving remission include maximizing the dose as tolerated, switching to a different class ifindicated, augmenting a partial response, or combining antidepressants when needed.


Table 4. Common Side Effects (SEs) for Antidepressant Medications

MEDICATION COMMON SIDE EFFECTS*

SSRIsCitalopramFluoxetineParoxetineSertralineFluvoxamine

Dizziness, dry mouth, insomnia, agitation,nausea, sexual dysfunction, headache

Bupropion SRBupropion (immediate release)

Headache, agitation, weight loss, insomnia,nausea

Nefazodone Dizziness, headache, nausea, somnolence,insomnia

Venlafaxine XRVenlafaxine

Dizziness, somnolence, insomnia, decreasedappetite, anxiety, headache, nausea, sexualdysfunction

TCAsAmitriptylineClomipramineDesipramineImipramineNortriptyline

Sedation, dizziness, dry mouth, nausea,insomnia, anxiety, anticholinergic effects,tremor, constipation, blurred vision,arrhythmias

Amoxapine Sedation, dizziness, dry mouth, nausea,anticholinergic effects, anxiety, insomnia,extrapyramidal reactions, seizures

Mirtazapine Dizziness, diarrhea, increased appetite,drowsiness, dry mouth

MAOIsPhenelzineTranylcypromine

Restlessness, dizziness, blurred vision,diarrhea, insomnia, weakness, arrythmias,headache, sexual dysfunction

* For complete side effects information, consult with the official product labeling or contact your MDD projectconsultants.


Table 5: Antipsychotic Dosing for Treatment of Psychotic Depression

Type/Class

Medication

Target Dose

(Level)

Maximum Dose

(Level)


Schedule Atypicals

Olanzapine (Zyprexa) Risperidone (Risperdal) Quetiapine (Seroquel)

10–15 mg

2–4 mg 100–800 mg

20 mg 6 mg

800 mg

qHS

bid or qHS

High potency

Haloperidol (Haldol)

2–5 mg

5–15 mg

QHS

Medium potency

Perphenazine (Trilafon)

8–16 mg

64 mg

QHS

Also refer to the Antipsychotic Monographs section in the Appendix.

Table 6: Common Side Effects (SEs) of Antipsychotic Medications

Antipsychotic EPS Sedation TardiveDyskinesia

AnticholinergicEffects

BloodPressure

SexualDysfunction

WeightGain

Clozapine(Clozaril) +/- ++++ - ++++ +++ + ++++

Haloperidol(Haldol) ++++ + ++++ + + + +

Olanzapine(Zyprexa) + ++ + ++ + - +++

Risperidone(Risperdal) ++ + + + + + ++

Quetiapine(Seroquel) +/- ++ ? +/- ++ - ++

- = none + = mild +/- = mild to none ++ = moderate +++ = moderately severe +++ = severe

Treatment of Psychotic Depression

• Combination treatment with an antidepressant and antipsychotic agent has been shown to be significantly moreeffective than either given alone.

• Currently the majority of data in the treatment of psychotic depression has been demonstrated with tricyclicantidepressants and conventional antipsychotics, but data evaluating combinations of newer antidepressants andatypical antipsychotics is accumulating.

• The advent of atypical antipsychotics has greatly increased treatment options.

• Advantages of atypical antipsychotics include a) lower incidence of extrapyramidal symptoms (EPS), b) broaderefficacy profile, and c) minimal impact on prolactin concentrations with olanzapine and quetiapine.


Table 7: Augmentation Dosing for Inadequate Response

Type/Class Medication Target Dose(Blood Level)

Maximum Dose(Blood Level)


ScheduleLithium 600–1200 mg

(0.4–0.6 mEq/L)1200–1800 mg

(0.8–1.0 mEq/L)BID

T3– Cytomel 25–50 micrograms 50 micrograms QAM

RecommendedAugmentation

Agents

Buspirone 25–50 mg 45–60 mg BID-TID

Dextroamphetamine 5–30 mg 60 mg QAMOtherAugmenting

Agents Methylphenidate 5–30 mg 40–60 mg BID

Also refer to the Monographs for Augmentation Agents section in the Appendix.

Table 8: Common Side Effects of Augmentation Agents

Medication Side Effects at Therapeutic Blood Level

Lithium Cognitive impairment TremorDrowsiness Muscle weaknessNausea/vomiting ThirstPolyuria

Buspirone Dizziness Nausea/vomitingInsomnia Dry mouthNervousness

Cytomel Insomnia DiarrheaTremor Increased/decreased appetiteHeadache Heat intoleranceNausea

Treatment of Depression using Augmentation Therapy

• In randomized controlled trials, at least 30% of depressed patients fail to respond to first-line antidepressanttreatment, despite adequate dose, duration, and compliance.

• Up to 21% of patients with major depression who seek treatment have not recovered after two years.

• Augmentation of treatment can result in a more rapid response to antidepressant medication. Studies have shownthat, among partial responders to serotonin reuptake inhibitors, patients demonstrate a higher recovery rate withaugmented antidepressant therapy in comparison to antidepressant treatment alone, as assessed by scores onstandardized depression rating scales.

• When an antidepressant medication elicits only partial response (25–75%), augmentation agents can potentiatean improved response, thus preventing the necessity of discontinuing the initial antidepressant.


Table 9: Dosing of Medications for Treatment of Associated Symptoms of Depression

Associated Symptom Medication Usual Dose range,mg/day Schedule

Insomnia

Lorazepam Clonazepam Zolpidem Trazodone

0.5–2.0 mg 0.5–2.0 mg 5–10 mg 25–100 mg

QHS; taper after7-10 days or assoon as possible

Anxiety

Lorazepam1

Alprazolam Clonazepam

0.5–4.0 mg 0.75–4.0 mg 1.5–3.0 mg

Q4–6h prnthroughout theday

Anxiety (if history of substanceabuse or if benzodiazepines arecontraindicated)

Buspirone

15–60 mg

BID-TID

Severe Agitation

Lorazepam Clonazepam Alprazolam Propranolol

0.5–2.0 mg 0.5–2.0 mg 0.75–4.0 mg 10–30 mg

QD

Table 10: Dosing of Medications for Treatment Emergent Side Effects

Treatment Emergent SideEffect Medication Usual Dose Range

(mg/day) Schedule

Insomnia Due to Medication (especially SSRI, BUP, orVLF)

Lorazepam1

Clonazepam Zolpidem Trazodone

0.5–2.0 mg 0.5–2.0 mg 5–10 mg 25–100 mg

QHS; taper assoon as possible

EPS from Antipsychotic Benztropine 2–4 mg QHS or BID Sexual Dysfunction Bupropion

Amantadine Methylphenidate

OR Consider switchto agent with lowsexual side effects

75 mg 100–200 mg 10–15 mg → bupropion,nefazodone, ormirtazapine

QD

1 In general, treatment emergent side effects should be addressed first by dose reduction or medication switching,as pharmacological intervention may increase the risk of drug interaction and additional adverse effects, thusdecreasing patient compliance.

2 Benzodiazepines are best avoided in patients with prior history of substance abuse/dependence or who are at riskfor substance abuse. Nonaddicting agents such as zolpidem or buspirone may be preferred.


Table 11: Guidelines for Switching Between Antidepressant Medications

FROM TO PLAN

SSRI SSRI ♦ Discontinue SSRI #1 and begin SSRI #2, or♦ Taper SSRI #1 and initiate SSRI #2.

SSRI TCABupropion

♦ Discontinue SSRI and begin TCA or bupropion, or♦ Taper SSRI and initiate TCA or bupropion gradually as tolerated to

therapeutic dose range.SSRI Nefazodone

Venlafaxine♦ Discontinue SSRI and begin nefazodone or venlafaxine, or♦ Taper SSRI and initiate nefazodone or venlafaxine gradually as

tolerated to therapeutic dose range.SSRI MAOI ♦ Discontinue SSRI. After a 5-week washout period for fluoxetine or a

2-week washout period for sertraline, paroxetine or citalopram,MAOI therapy can safely be initiated.

TCAVenlafaxineNefazodoneBupropion

TCA ♦ Discontinue TCA #1 (or venlafaxine, nefazodone, bupropion) bytaper and then initiate TCA #2, or

♦ Taper TCA #1 (or venlafaxine, nefazodone, bupropion) whileinitiating TCA #2 gradually as tolerated to therapeutic dose range.


SSRI ♦ Taper and discontinue TCA (or venlafaxine, nefazodone, bupropion)and then initiate SSRI, or

♦ Taper TCA (or venlafaxine, nefazodone, bupropion) while initiatingSSRI at a low dose.


NefazodoneVenlafaxineBupropion

♦ Discontinue TCA (or venlafaxine, nefazodone, bupropion) andinitiate nefazodone, venlafaxine, or bupropion, or

♦ Taper and discontinue TCA (or venlafaxine, nefazodone, bupropion)to initiate nefazodone, venlafaxine, or bupropion gradually astolerated to therapeutic dose range.

TCA MAOI ♦ Discontinue TCA. After a 2-week washout, MAOI therapy can besafely initiated.

MAOI MAOINefazodoneVenlafaxineBupropion

♦ Discontinue MAOI #1. After a 2-week washout, therapy with MAOI#2 (or TCA, venlafaxine, nefazodone, or bupropion) can be safelyinitiated.

Also refer to the Guidelines for Switching Between Antidepressant Medications in the Appendix for case examples.

These principles apply to the tactics of switching antidepressant medications, depending on the reasons forswitching and on the duration of exposure to the first agent.

• If the first antidepressant is being discontinued due to intolerance following a brief exposure (< 7 days), it can bestopped and the second drug started.

• If the first drug is being discontinued after a longer exposure (> 7 days), due to symptomatic breakthrough, orinadequate response, then it should be tapered and the second drug started gradually (notable exception being aswitch from an MAOI).


• Serotonin discontinuation syndrome can occur following abrupt cessation of antidepressant therapy,particularly for those antidepressants with shorter half-lives (sertraline, paroxetine, fluvoxamine, citalopram) orno active metabolites. The syndrome is characterized by dizziness, insomnia, nervousness, nausea, andagitation. Initiating a medication taper does not always prevent its occurrence but may minimize severity.


Table 12: Guidelines for Combining Antidepressant Medications

Combination Plan

SSRI with TCA ♦ Because SSRIs markedly increase blood levels of TCAs upto values exceeding therapeutically recommended ranges,serum levels of TCA should be monitored throughouttreatment and adjusted accordingly.

SSRI with Bupropion SR ♦ Monitor for agitation.

SSRI with Nefazodone ♦ Initiate low dose of nefazodone as an addition to SSRItreatment, then gradually increase to therapeutic dose range.Monitor for increased side effects.

Other Combinations1

Bupropion SR with NefazodoneVenlafaxine with Mirtazapine

♦ Monitor side effects.

1 No systematic studies available as yet.

Combining Antidepressants for Treatment of Depression

• Treatment-resistant depression (TRD) is defined as depression that is resistant to two courses of monotherapywith pharmacologically different antidepressants given in an adequate dose for a sufficient length of time.

• It is estimated that about 20% of depressed patients are resistant to monotherapy. Several studies have reportedthe efficacy of combining two antidepressants to treat patients with TRD.

• In general, because of the potential for drug interactions, antidepressant combination treatment should be usedcarefully, and patients monitored closely. The goal of combination antidepressant regimens is to combinemedications to theoretically enhance clinical response.

• Stage 5 of the algorithm recommends combining two antidepressants. The medications should be initiatedsimultaneously at a low dose, then titrated upwards gradually to a therapeutically recommended dose.

• If a TCA is being used in combination treatment, plasma levels should be monitored.

• Because there is a risk of developing Serotonin Syndrome with combination antidepressant therapy, patientsshould be monitored for signs of confusion, disorientation, agitation, restlessness, diaphoresis, diarrhea, ataxia,and hyperreflexia.


Algorithm Implementation

The purpose of treatment algorithms is to integrate available research information and clinical experienceinto the development of user-friendly, step-by-step "preferred practices," medication guidelines, ormedication algorithms. Algorithms do not decrease the need for clinicians having adequateeducation and clinical training, nor are they intended to restrict treatment options. Rather, they aredesigned to facilitate a systematic approach to recommended treatment interventions.

It is assumed that a comprehensive psychiatric evaluation, a complete general medical history, andrelevant diagnostic tests are completed prior to entry into any treatment algorithm. Some patients may notbe appropriate for entry into the algorithms. In addition, patients may enter the algorithms at differentstages depending upon their specific clinical features and previous treatment histories. For example,patients may enter Stage 2 or 3 if they have already failed to respond to an adequate trial of anotherantidepressant monotherapy.

Treatment algorithms are not a substitute for clinical assessment or clinical judgment. They aretools to assist clinicians in making clinical decisions to optimize therapeutic outcomes. Thepurpose of this document is to amplify the steps in implementing a medication algorithm in orderto maximize effectiveness. We describe issues related to the strategic choices forpharmacological interventions based on the TMAP Depression Algorithm. Additionally, preferredtactical steps and critical decision points are described to enable users to best apply the strategyselected for implementation.

These algorithms focus on the pharmacotherapy and patient/family education for major depressivedisorder. This does not imply that other nonpharmacological treatments including psychotherapy andrehabilitation are not indicated for the treatment of major depressive disorder (MDD). Instead, thisalgorithm is restricted to a single focus: a multi-step medication approach in the treatment of patients withMDD in the public sector. Other modalities used in the treatment of mental disorders are sufficientlycomplex that it is felt that patient care in TDMHMR can be best enhanced, initially, by utilizing algorithmsthat focus on one major aspect of treatment — in this case the use of pharmacological interventions.Additionally, patient and family education packages (ED packages) are also included in the overallprotocol, since it is felt that proper implementation of the medication algorithm is enhanced through activeparticipation of patients and families. Subsequent iterations may include psychological and rehabilitativeservices in the treatment package(s).

General Medical Principles Guiding Algorithm Implementation:

Treatment Goals1. The ultimate goal in the acute phase of treatment (0–12 weeks) is achieving symptomatic remission

and full return of psychosocial functioning. The prevention of relapse and recurrence is the essentialgoal of the continuation and maintenance phases of treatment.

Medication Phasing2. The treatment options recommended at various points in the algorithms are based upon available data

from: (a) controlled clinical trials [level A evidence]; (b) open trials and retrospective data analyses[level B evidence]; and (c) case reports and clinical consensus [level C evidence]. The later stages inthe algorithm involve more complicated single or combined regimens, while the earlier stages involvesimpler, more routine medications in terms of safety, ease of use, side effect profiles, etc.


Previous History3. A patient's previous response to antidepressant treatments should always be considered when

selecting the point of entry into an algorithm. If a patient responded well to a specific pharmacotherapyor other treatment intervention during a previous episode of depression, the same treatment should beused again. Similarly, if a patient failed to respond, or was unable to tolerate an adequate trial of aspecific medication during a previous episode of depression, that medication is not recommended forthe current or future depressive episodes.

Physician-Patient Team4. An adequate discussion between the clinician and the patient regarding available treatment options

and information concerning specific medications (including expected results, routine dosing strategies,possible side effects, drug interactions, as well as potential toxicity in overdose) is essential.Medication selection should be dependent on these factors. When these considerations suggest thatseveral medications are equivalent, patient preference becomes paramount and should define theparticular option selected. It has been well documented that patient participation during this process islikely to enhance compliance to the chosen treatment option.

Entering the Algorithm5. Eligibility and point of entry into the algorithm for an individual patient should be determined by the

physician based upon a review of relevant psychiatric factors (e.g., symptom severity, suicidality,comorbidity, etc.), medical status (e.g., concomitant medications or illnesses, age, etc.), and priortreatment history. A rationale should be provided when a patient enters the algorithm at a laterpoint/stage or when stages in the algorithm are skipped.

Visit Frequency6. At the beginning of each stage, weekly contact is recommended (office visit or by phone) for the first 4

weeks; then every other week until 50% improvement in symptoms is attained for at least 4 weeks;then once per month until 75% improvement has been attained for at least 4 weeks. After 75%improvement has been reached, visits may be scheduled monthly and then every 3 months as thepatient moves into the maintenance phase of treatment. Increased visit frequency is recommended inan attempt to optimize treatment outcomes by: a) encouraging patient adherence with treatment andb) rapidly identifying and correcting potential problems or adverse events associated with treatment(e.g., worsening of depression, potential suicidal ideology, etc.). Support personnel may contactpatients by phone if the physician is unable to see them.

Treatment Duration7. Response to a medication is enhanced by ensuring an adequate treatment trial of at least 4–8 weeks

of administration at the recommended dose range. However, if a patient fails to respond to anadequate dose of a specific medication for 4–6 weeks or has an unsatisfactory or partial response byweeks 6–8, an alternative treatment plan is recommended. The duration of a treatment trial may beextended to 8–12 weeks if an augmentation strategy has been instituted in patients with a partialresponse.

Continuation Phase8. Continuation phase treatment is recommended to prevent relapse for all patients with major

depressive disorder who achieve a satisfactory clinical response, preferably symptom remission. Aftera full response, the medication(s) should be continued for 6–9 months at the dose effective during theacute phase. Patients should be evaluated at least once every 3 months during continuation treatment


(preferably every 1–2 months). Interim phone calls are also recommended one week beforemedication refills to enhance adherence.

Maintenance Phase9. Maintenance phase treatment is recommended for patients with major depressive disorder who: a)

have had at least three episodes of major depression, or b) have experienced two episodes of majordepression and have additional factors that contribute to an increased risk of recurrence (e.g.,comorbid anxiety disorder or substantial residual functional impairment). Maintenance medicationshould be continued at full therapeutic doses and, as in the continuation phase, the regimenassociated with symptom remission is recommended. The optimal duration of maintenance treatmenthas not been established, but depending on risk factors, is generally between one year pastcontinuation phase and lifetime administration. Patients should be evaluated every 3–6 months duringmaintenance treatment.

Lack of Significant Improvement Despite Treatment10. A Structured Clinical Interview for DSM-IV (SCID) or further evaluation of symptoms should be

considered:a) to confirm a diagnosis.b) to reconfirm the diagnosis if there has been no response after 3 months.c) if comorbid psychiatric conditions are present.d) if patient has failed on 2 different classes or stages of medications.

Documentation11. Adequate documentation should be completed for each algorithm stage and treatment choice or

critical decision point. If algorithm stages are skipped or if treatment deviates from the algorithmrecommendations, the rationale behind the decision should be adequately documented.

Psychotherapy12. At baseline and throughout treatment, possible psychosocial interventions, including psychotherapy,

should be considered to optimize treatment. The protocol allows for the addition of psychotherapy ifclinically indicated based on individual patient situations.

Treatment of Associated Symptoms and Side Effects13. Adjunctive medications prescribed for the treatment of associated symptoms such as anxiety or

treatment emergent side effects should be discontinued once these symptoms resolve. It shouldalways be remembered that the prescription of additional medication also carries the risk of increasedside effects. The rationale for their use should be carefully documented. The continued indication forthese medications should be re-assessed on a regular basis.


Critical Decision Pointsfor the Nonpsychotic Depression Algorithm

Critical Decision Points (CDPs) are designed to prompt an assessment of symptoms and a determinationof a need for a change in strategy or tactics. At each CDP, the physician should assess the patient forimprovement and make a decision to either continue or change treatment based on improvement insymptoms or lack thereof. Note: Patients begin at CDP # 1 at the beginning of each stage.

STAGES 1,2,3

Patients entered into one of these stages will be placed on a monotherapy treatment regimen. Thesemedications are staged in the algorithm according to efficacy, side effect profile, and ease of use.Placement in the algorithm should be determined by the patient and physician based on prior history ofantidepressant use, clinical presentation, and personal preferences.

Patients should return to the clinic or be contacted by clinic personnel weekly (office visit or byphone) for the first 4 weeks of each treatment stage and then every 2 weeks until 50%improvement in symptoms is maintained for at least one month. Patients will then be evaluatedmonthly until 75% improvement is maintained for at least one month. Support personnel maycontact patients by phone if the physician is unable to see them.

CDP # 1, Week 0

Inclusion Criteria:Patients entering Stages 1, 2, or 3 of the nonpsychotic algorithm should have a diagnosis of majordepressive disorder of sufficient severity to merit medication treatment and they a) have not beenon any antidepressant medication for the current episode of MDD or b) need a medication changeto another monotherapy antidepressant.

Treatment Options:

Stage 1:• Selective Serotonin Reuptake Inhibitors (SSRIs) - citalopram, fluoxetine, paroxetine, sertraline• Venlafaxine XR• Bupropion SR• Nefazodone• Mirtazapine

Stage 2:• Selective Serotonin Reuptake Inhibitors (SSRIs) - citalopram, fluoxetine, paroxetine, sertraline• Venlafaxine XR• Bupropion SR• Nefazodone• Mirtazapine• Tricyclic Antidepressants – desipramine, nortriptyline, etc. Note: In general, secondary

amines should be tried before tertiary amines.


Stage 3:• Selective Serotonin Reuptake Inhibitors (SSRIs) - citalopram, fluoxetine, paroxetine, sertraline• Venlafaxine XR• Bupropion SR• Nefazodone• Mirtazapine• Tricyclic Antidepressants – desipramine, nortriptyline, etc. Note: In general, secondary

amines should be tried before tertiary amines.• MAOIs

CDP # 2, Week 4 Stages 1, 2, and 3 Nonpsychotic MDDSymptom Improvement (SEs tolerable)

0-50% Gradually increase dose as tolerated for an additional 2 weeks.

50-75% Continue current dose, orGradually increase dose as tolerated for an additional 2 weeks.

75-100% Go to Continuation if 75% improvement for at least 4 weeks.Otherwise, continue current dose.

Improved, but SEs areintolerable

Continue current dose and address SEs, orDecrease dose and continue for 2 additional weeks, orGo to the next stage.

Not improved and SEs areintolerable Go to the next stage.

Return to clinic: Return in 2 weeks.

CDP # 3, Week 6 Stages 1, 2, and 3 Nonpsychotic MDDSymptom Improvement (SEs tolerable):

0-25%Strongly consider augmenting (refer to the Guidelines forAugmentation Therapy in the Appendix), orGo to the next stage.

25-50%If dose was not increased at Week 4, increase dose, orIf dose was increased at Week 4, augment or continue withcurrent treatment.

50-75% Increase dose, orConsider augmentation.



Continue current dose and address SEs, orDecrease dose and continue for 2 additional weeks, orGo to the next stage.


Return to clinic: If > 50% improvement for 1 month, return in 4 weeks.Otherwise, return in 2 weeks.


CDP # 4, Week 8 Stages 1, 2, and 3 Nonpsychotic MDDSymptom Improvement (SEs tolerable):0-25% Increase augmentation, or

Go to the next stage.

25-50% Augment, if not done previously, orGo to the next stage.

50-75% Maximize dose, if not done previously, orConsider augmentation.


SEs are intolerable Go to the next stage.



0-25% Go to the next stage.

25-50% Increase augmentation.

50-75% Increase augmentation, orGo to the next stage.










Stage 4

Clinical trials suggest that at least 30% of depressed patients fail to respond to first-line antidepressanttreatment, despite adequate dose, duration, and compliance. In addition, up to 21% of patients with majordepression who seek treatment have not recovered after two years. Clinicians have developed variouspharmacological strategies to treat such refractory depression, including augmentation of therapy withthyroid (T3 - Cytomel) medication, lithium, or buspirone. Studies have shown that, among nonrespondersto serotonin reuptake inhibitors, patients demonstrate a higher recovery rate with augmentedantidepressant therapy in comparison to antidepressant treatment alone, as assessed by scores onstandardized depression rating scales. These augmentation strategies have clearly illustrated an efficacyand clinical utility, possibly resulting in complete or near-complete recovery in up to 60% of cases.

CDP # 1, Week 0

Inclusion Criteria:Stage 4 includes patients from Stages 1–3 who a) did not have a full response or b) were unable totolerate side effects. Patients may enter at or skip to Stage 4 if their previous history or currentcondition suggests that Stage 4 is most clinically appropriate.

Treatment Option:An antidepressant, preferably from a different class not tried in Stages 1–3, augmented by eitherlithium, buspirone, or a thyroid agent. Both medications should be started at the same time,following critical decision points on the CDP Table (Table 2, page 10) and the CDP Flowchart,page 7. If lithium augmentation was not used in a previous stage, consider using it here due toLevel A evidence of lithium augmentation.

CDP # 2, Week 4 Stage 4 Nonpsychotic MDDSymptom Improvement (SEs tolerable):

0-50%

Gradually increase antidepressant dose as tolerated andcontinue for an additional 2 weeks and/or increase the dose ofthe augmenting agent. See Table 3 on page 11 and Table 7 onpage 14 for dosing.Note: A gradual dose increase is critical for the Stage 4antidepressants since response is enhanced by titration within atherapeutic dose range.

50-75% Continue current dose(s), orGradually increase the dose(s) as tolerated.



Continue current dose(s) and address side effects, orDecrease dose(s) and continue, orGo to the next stage.




CDP # 3, Week 6 Stage 4 Nonpsychotic MDDSymptom Improvement (SEs tolerable):0-25% Maximize the antidepressant dose and/or augmentation dose.

25-50%Maximize the antidepressant dose and attain lithium serumlevels of 0.8–1.2 mEq/L or the maximal therapeutic dose for theselected augmentation strategy.

50-75%

Continue with current dose(s), orGradually increase the antidepressant dose, orIf already at maximum dose of the antidepressant, increase thedose of augmentation dose (if not at maximum).


Improved, but SEs areintolerable:





0-50% Increase augmentation dose, if not at maximum.

50-75%If patient is at maximal tolerable therapeutic dose, consider analternative augmenting agent, orContinue with current dose(s).







CDP # 5, Week 10 Stage 4 Nonpsychotic MDDSymptom Improvement (SEs tolerable):0-25% Go to the next stage.

25-50% Increase augmentation dose.

50-75%

Maximize the antidepressant dose and increase augmentationdose to achieve a lithium steady-state serum concentration of0.8–1.2 mEq/L or the maximal therapeutic dose for the selectedaugmentation strategy, orIf the patient is receiving the maximal therapeutic lithium oralternative augmentation agent dose, go to the next stage.






50-75%

Maximize the antidepressant dose and maximize augmentationdose to achieve a lithium steady-state serum concentration of0.8–1.2 mEq/L or the maximal therapeutic dose for the selectedaugmentation strategy, orIf the patient is receiving the maximal therapeutic lithium oralternative augmentation agent dose, go to the next stage.





Stage 5

Treatment-resistant depression (TRD) is defined as depression that is resistant to two courses ofmonotherapy with pharmacologically different antidepressants given in adequate doses for sufficientlengths of time. It is estimated that about 20% of depressed patients are resistant to monotherapy.Several studies have reported the efficacy of combining two antidepressants to treat patients with TRD.

CDP #1, Week 0

Inclusion Criteria:Stage 5 includes patients who did not have a full response during Stage 4 or who had intolerableside effects.

Treatment Options:Antidepressant combination therapy may be considered if patients have failed to respond inprevious stages. If a TCA or SSRI is being used as monotherapy, consider a TCA/SSRIcombination [level B evidence]. Both antidepressants should be initiated simultaneously. Since theSSRIs — particularly fluoxetine and paroxetine — may inhibit the metabolism of TCAs, closemonitoring of TCA serum concentrations should occur during TCA/SSRI combination treatment[level A evidence]. Because of norfluoxetine's long elimination half-life, maximum effects offluoxetine on elevation of the TCA serum concentrations may not be observed for 4–6 weeks. If aTCA is added to an SSRI, it will not take this long, as maximal enzyme inhibition will have alreadyoccurred and time to steady state is dependent on the particular TCA used. The goal is to obtaintwo serial TCA levels — at least one week apart — that are essentially the same. Since evidencefor the efficacy of other antidepressant combinations are derived entirely from case series, they arerecommended only as additional options at this stage.

In general, because of the potential for drug interactions, antidepressant combination treatmentshould be used carefully, and patients monitored closely. The goal of combination antidepressantregimens is to combine medications to theoretically enhance clinical response.

Considerable care is required to obviate potential drug interactions associated with combinedregimens. Table 12 on page 18 is provided as a guideline for the tactic of antidepressantcombinations. Other treatment tactics included in Stage 5 are identical to those outlined in Stage 4.



0-50% Gradually increase dose(s) as tolerated for an additional 2weeks.

50-75%Continue current dose(s), orGradually increase dose(s) as tolerated for an additional 2weeks.



Continue with current dose(s) and address side effects, orDecrease dose(s) and continue, orGo to the next stage.





50-75%

Continue current dose(s), orGradually increase dose(s) as tolerated for an additional 2weeks, orIncrease to maximum therapeutic dose(s) and continue tomonitor for an additional 2 weeks.







0-75% Consult with the Project Director, orGo to the next stage.








0-75% Consult with the Project Director, orGo to the next stage.






CDP # 6, Week 12Symptom Improvement (SEs tolerable):






Stage 6

Electroconvulsive therapy (ECT) has been shown to be an effective treatment option for mentally illpatients who are nonresponders to antidepressant medications or intolerant of the side effects. Patientgroups expected to be favorable responders to ECT are manic-depressive and psychotic depressivepatients. The antidepressive effects of ECT are immediate and comprehensive, and can elicit animproved response from medication when used in combination. Schizophrenia patients have also derivedbenefits from ECT therapy, when administered concurrently with antipsychotic medication.

CDP #1, Week 0

Inclusion Criteria:Stage 6 includes patients who did not have a full response during Stage 4 or 5 or who were unableto tolerate side effects. Depending on a patient's current condition or past treatment history, apatient may initially enter the algorithm at Stage 6. For example, a severely depressed patient withsignificant risk of suicide should be considered for initial entry at Stage 6 — treatment with ECT.

Treatment Options:Stage 6 treatment is ECT. If the patient refuses ECT, or if ECT is unavailable or contraindicated,go to Stage 7.

As cognitive side effects are generally less severe compared with bilateral ECT, treatment maybegin with right unilateral ECT. However, before declaring a patient resistant to ECT, a course ofbilateral ECT should be considered. The electrical dose of right unilateral ECT should be at least2.5 times the initial seizure threshold, while bilateral ECT should be dosed no more than 1.5 timesthe initial threshold. ECT should be terminated when patients are in full remission or fail to sustainadditional improvement over 1–2 treatments. With either ECT modality, at least 6–10 ECTtreatments should be attempted before declaring a patient resistant to treatment. (Note: Avoid ECTwhen the patient is taking lithium because CNS lithium toxicity may ensue.)


Stage 7

Treatment-resistant depression (TRD) is defined as depression that is resistant to two courses ofmonotherapy with pharmacologically different antidepressants given in adequate doses for sufficientlengths of time. It is estimated that about 20% of depressed patients are resistant to monotherapy. If apatient has not attained complete remission of symptoms after adequate trials of medication treatment,then it may be necessary to accept partial response (25–75%) as a satisfactory outcome. The duration ofcritical decision points (CDPs) may need to be extended in order to allow slow responders a longer periodof time on their medication.

CDP # 1, Week 0

Inclusion Criteria:Stage 7 includes patients who fail to fully respond during Stages 1–6 (including patients whorefuse consent to ECT) or who are unable to tolerate side effects.

Treatment Options:Stage 7 includes the alternatives not used previously during earlier stages (e.g., olanzapine,lamotrigine or one of the newer antidepressants). It also includes other antidepressantcombinations (not included in Stage 5) that are more speculative than those previously discussedin earlier stages. Alternative augmenting agents such as T3, buspirone, and methylphenidate arealso included in Stage 7. At Stage 7, combinations of antidepressants or antidepressants plus analternative augmenting agent are preferable to a monotherapy not previously tried. Even thoughstage(s) can be skipped in the algorithm, Stage 7 is most likely to be indicated for those patientswho have already failed to respond to multiple earlier stages in the algorithm.

Antidepressant Switching Tactics:Because of the possibility of drug interactions, care should be taken when switching from oneantidepressant to another. Please refer to page 16 for guidelines concerning switching from oneantidepressant to another.






Continue with current dose(s) and address side effects, orDecrease dose(s) and continue, orConsider switching to an alternative medication. If beginning atrial of a second antidepressant, go back to CDP # 1; orConsult with the Project Director.

Not improved and SEs areintolerable Consult with the Project Director.




0-50%Consider switching to an alternative medication. If beginning atrial of an antidepressant, return to CDP # 1; orConsult with the Project Director.

50-75% Continue current dose(s), orGradually increase dose as tolerated for an additional 2 weeks.







0-50% Consult with the Project Director.

50-75% If patient is at maximum tolerable therapeutic dose(s), consultthe Project Director.








0-50% Consult with the Project Director.

50-75% If patient is at maximum tolerable therapeutic dose(s), consultthe Project Director.







0-75% Consult the Project Director.


SEs are intolerable Consult with the Project Director.



Critical Decision Points for the Psychotic Depression Algorithm

Critical Decision Points are designed to prompt an assessment of symptoms and a determination of aneed for a change in strategy or tactics. At each critical decision point or CDP, the physician shouldassess the patient for improvement and make a decision to either continue or change treatment based onimprovement in symptoms or lack thereof. Note: Patients begin at CDP # 1 at the beginning of eachstage.

Stage 1

The advent of a new generation of antipsychotic medications has opened up more treatment options forpsychiatrists in treating disorders with psychotic symptoms. The newer medications, signified as "atypical"antipsychotics, have several advantages to their predecessors and are more desirable candidates for thispatient population. These include: olanzapine (Zyprexa), risperidone (Risperdal), and quetiapine(Seroquel). Notable benefits include a lower incidence of extrapyramidal symptoms, a broader efficacyprofile — particularly with negative symptoms — and minimal impact on prolactin concentrations(olanzapine and quetiapine). Older antipsychotic agents have demonstrated a higher incidence ofproblematic side effects that hinder their use. Combination treatment with an antidepressant and anantipsychotic agent has shown to be significantly more effective than either given alone. Initial findingshave demonstrated this with tricyclics and conventional antipsychotics, and data evaluating combinationsof newer antidepressants and atypical antipsychotics are now accumulating.

Patients should return to the clinic or be contacted by clinic personnel weekly for the first 4 weeksof each treatment stage; then every other week until 50% improvement is maintained for at leastone month; then every 4 weeks until 75% improvement is maintained for at least one month.

CDP #1, Week 0

Inclusion Criteria:The patient entered into the algorithm at Stage 1 is most likely either experiencing his/her firstepisode of major depression complicated by psychotic features or has previously responded to aStage 1 regimen during a past episode.

Treatment Options:• A tricyclic antidepressant (TCA) [amitriptyline, clomipramine, desipramine, imipramine, or

nortriptyline] plus an antipsychotic [level A evidence], or• A Serotonin Selective Reuptake Inhibitor (SSRI) plus an antipsychotic or venlafaxine XR plus

an antipsychotic, [level B evidence], or• Amoxapine [level A evidence].


CDP # 2, Week 4 Stage 1 Psychotic MDDSymptom Improvement (SEs tolerable):





Continue current dose(s) and address side effects, orDecrease dose of drug thought to be causing side effect (i.e.,antidepressant or antipsychotic) and continue for 2 additionalweeks, orGo to the next stage.




0-25%Strongly consider augmenting (refer to the Guidelines forAugmentation Therapy in the Appendix), orGo to the next stage.

25-50%If dose(s) were not increased at Week 4, increase dose(s).If dose(s) were increased at Week 4, augment or continue withcurrent treatment.

50-75% Increase dose(s), orConsider augmentation.



Continue current dose(s) and address side effects, orDecrease dose(s) and continue for 2 additional weeks, orGo to the next stage.





25-50% Augment if not done previously, orGo to the next stage.

50-75% Increase dose(s), orConsider augmentation.





CDP # 5, Week 10 Stage 1 Psychotic MDDSymptom Improvement (SEs tolerable):0-25% Go to the next stage.













Stage 2

CDP #1, Week 0

Inclusion Criteria:Stage 2 includes patients who did not have a full response at Stage 1 or who were unable totolerate side effects. Patients may enter the algorithm at Stage 2 if their history of response duringprevious depressive episodes suggests that Stage 1 is not appropriate. If the patient's clinicalpresentation dictates a need for more immediate clinical response (e.g., emergent suicidality) or ifthe patient has a history of previous response to ECT, entry at Stage 3 should be considered.

Treatment Options:1. Patient did not have full response at Stage 1.

a) If the patient received a TCA during Stage 1 and did not respond, consider venlafaxine XR(increase the dose to > 225 mg/d) with an antipsychotic or proceed to Stage 3 (ECT).

b) If an SSRI was the antidepressant used in Stage 1, consider a TCA with an antipsychotic.c) If amoxapine was the antidepressant used in Stage 1, consider a TCA with an antipsychotic.


2. If the patient did not respond during Stage 1 due to intolerable side effects, select anantidepressant from a different class than the previous choice and with a contrasting side effectprofile (e.g., from a TCA to an SSRI). If a patient is unable to tolerate 2 different antidepressantmonotherapies from distinct chemical classes, consider proceeding to Stage 3.

3. The tactics for drug treatment in Stage 2 are essentially the same as those outlined in Stage 1.Patients should be initiated with doses of antidepressants at the lower end of the therapeuticrange and the dose gradually increased as tolerated if response is not attained. Patients shouldbe seen and monitored frequently during the initial month. At week 4, if full response is absent,response and medication tolerability should be assessed. Further assessments at subsequentcritical time points on a 2-week basis should be completed to assess for dose increase asoutlined in treatment tactics (see Table 2).


0-50% Increase antidepressant dose to a maximal therapeutic leveland continue for two additional weeks.

50-75%Continue current antidepressant dose, orGradually increase antidepressant dose as tolerated to amaximal therapeutic range.

75-100% Go to Continuation if 75% improvement for at least 4 weeks.Otherwise, continue current antidepressant dose.


Continue current antidepressant dose and address side effects, orDecrease antidepressant dose and continue for 2 additionalweeks, orGo to the next stage.




0-50%

If the antidepressant dose was maximized at week 4, go to thenext stage; orIf the antidepressant dose was not maximized at week 4,increase the dose to the maximum therapeutic level (monitorserum concentration for TCAs).

50-75%Continue current antidepressant dose, orGradually increase antidepressant dose as tolerated to amaximal therapeutic range.



Continue current antidepressant dose and address side effects, orDecrease antidepressant dose and continue for 2 additionalweeks, orGo to the next stage.






50-75% Continue at maximal doses for 2 additional weeks.










Stage 3

ECT has been shown to be an effective treatment option for mentally ill patients who are nonrespondersto antidepressant medications or intolerant of the side effects. Patient groups expected to be favorableresponders to ECT are manic-depressive and psychotic depressive patients. The antidepressive effectsof ECT are immediate and comprehensive, and can elicit an improved response from medication whenused in combination. Schizophrenia patients have also derived benefits from ECT therapy, whenadministered concurrently with antipsychotic medication.

Inclusion Criteria:Stage 3 includes patients who did not have a full response at Stage 2 or who were unable totolerate side effects. Patients may enter the algorithm at Stage 3 if their current condition,associated features, or history of response during a previous depressive episode suggest thatStage 1 or 2 is not appropriate or is contraindicated. If the patient's clinical presentation warrants amore immediate clinical response (e.g., emergent suicidality) or history of previous response toECT, entry at Stage 3 should be considered.

Treatment Options:• Stage 3 treatment is ECT.

As cognitive side effects are generally less severe compared with bilateral ECT, treatment maybegin with right unilateral ECT. However, before declaring a patient resistant to ECT, a course ofbilateral ECT should be considered. The electrical dose of right unilateral ECT should be at least2.5 times the initial seizure threshold, while bilateral ECT should be dosed no more than 1.5 timesthe initial threshold. ECT should be terminated when patients are in full remission or fail to sustainadditional improvement over 1–2 treatments. With either ECT modality, at least 6–10 ECTtreatments should be attempted before declaring a patient resistant to treatment. (Note: AvoidECT when the patient is taking lithium because CNS lithium toxicity may ensue.)

• In general, any antidepressant or antipsychotic medication should be discontinued beforeinitiating ECT.

• If a patient does not give informed consent for ECT, fails to respond to ECT, or ECT is notavailable, proceed to Stage 4.


Stage 4

Clinical trials suggest that at least 30% of depressed patients fail to respond to first-line antidepressanttreatment, despite adequate dose, duration, and compliance. In addition, up to 21% of patients with majordepression who seek treatment have not recovered after two years. Clinicians have developed variouspharmacological strategies to treat such refractory depression, including augmentation of therapy withthyroid (T3 - Cytomel) medication, lithium, and buspirone. Studies have shown that, among partial-responders to serotonin reuptake inhibitors, patients demonstrate a higher recovery rate with augmentedantidepressant therapy in comparison to antidepressant treatment alone, as assessed by scores onstandardized depression rating scales. These augmentation strategies have clearly illustrated an efficacyand clinical utility, possibly resulting in complete or near-complete recovery in up to 60% of cases.

CDP #1, Week 0

Inclusion Criteria:Stage 4 includes patients from Stage 3 who a) did not have a full response or b) were unable totolerate side effects. Patients may enter or skip to Stage 4 if their previous history or currentcondition suggests that Stage 4 is most clinically appropriate.

If the patient did not have a full response to any of the combinations in Stages 1 or 2, Stage 4should be completed prior to beginning Stage 5.

Treatment Options:At least one attempt at lithium augmentation should be initiated (unless contraindicated) beforeproceeding to Stage 5. Both the antidepressant and the augmenting agent should be startedsimultaneously.

If the patient fails an adequate trial of lithium augmentation (or is unable to tolerate lithium),alternative augmenting agents such as T3 or buspirone should be strongly considered.


0-50% Increase antidepressant dose to a maximal therapeutic leveland continue for two additional weeks.

50-75%

Continue current dose(s), orGradually increase dose(s) as tolerated to a range of 0.4–0.8mEq/L for lithium or the maximal therapeutic dose for theselected augmentation strategy and to the therapeutic rangeappropriate for the antidepressant.



Continue current dose(s) and address side effects, orDecrease dose(s) and continue for 2 additional weeks, orGo to the next stage.





0-50%

If the antidepressant dose was already maximized at week 4,increase the lithium dose so that serum levels between 0.8–1.2mEq/L are attained or the maximal therapeutic dose for theselected augmentation strategy; orIf the antidepressant dose was not maximized at week 4 and thepatient is currently tolerating the antidepressant, the doseshould be increased to the usual maximum dose (monitor serumconcentration for TCAs).

50-75%

If the antidepressant dose was maximized at week 4, continuecurrent dose(s) for an additional 2 weeks; orMaximize the antidepressant dose within the therapeutic rangeand the lithium dose should be increased to 0.8–1.2 mEq/L orthe maximal therapeutic dose for the selected augmentationstrategy for an additional 2 weeks.

75-100% Go to Continuation if 75% improvement for at least 4 weeks.Otherwise, continue current dose(s).


Continue current dose(s) and address side effects, orDecrease dose(s) and continue for 2 additional weeks, orConsider switching medications if side effects are attributable toa particular medication, orGo to the next stage.






75-100% Go to Continuation if 75% improvement for at least 4 weeks.Otherwise, continue current doses.









Stage 5

Treatment-resistant depression (TRD) is defined as depression that is resistant to two courses ofmonotherapy with pharmacologically different antidepressants given in an adequate dose for a sufficientlength of time. It is estimated that about 20% of depressed patients are resistant to monotherapy. If apatient has not attained complete remission of symptoms after adequate trials of medication treatment,then it may be necessary to accept partial response (25–75%) as a satisfactory outcome. The duration ofcritical decision points (CDPs) may need to be extended in order to allow slow responders a longer periodof time on their medication.

CDP #1, Week 0

Inclusion Criteria:Stage 5 includes patients who fail to fully respond during Stages 1–4 or who are unable to tolerateside effects.

Treatment Options:Stage 5 includes the alternatives not used previously during earlier stages (e.g., lamotrigine or oneof the newer antidepressants). It also includes antidepressant combinations. Alternativeaugmenting agents such as T3 or buspirone should be strongly considered, and methylphenidate isalso included in Stage 5. Even though stage(s) can be skipped in the algorithm, Stage 5 ismost likely to be indicated for those patients who have already failed to respond to multipleearlier stages in the algorithm.


0-50% Increase antidepressant dose to a maximal therapeutic leveland continue for 2 additional weeks.

50-75%Continue current dose(s), orGradually increase dose(s) as tolerated to a maximaltherapeutic range.



Continue current dose(s) and address side effects, orDecrease dose(s) and continue for 2 additional weeks, orConsult Project Director.

Not improved and SEs areintolerable Consult Project Director.




0-50%

If the antidepressant dose was maximized at week 4, consultthe Project Director; orIf the antidepressant dose was not maximized at week 4,increase the dose to the usual maximum dose (monitor serumconcentration for TCAs).

50-75%

If the antidepressant dose was maximized at week 4, continuecurrent dose(s) for an additional 2 weeks; orMaximize the antidepressant dose within the therapeutic rangeand continue for an additional 2 weeks.

75-100% Go to Continuation if 75% improvement for at least 4 weeks.Otherwise, continue current dose(s).


Continue current dose(s) and address side effects, orDecrease dose(s) and continue for 2 additional weeks, orConsider switching medications if side effects are attributable toa particular medication, orConsult the Project Director.

Not improved and SEs areintolerable Consult the Project Director.







Continue current dose(s) and address side effects, orDecrease dose(s) and continue for 2 additional weeks, orConsider switching medications if side effects are attributable toa particular medication, orConsult the Project Director.

Not improved and SEs areintolerable Consult the Project Director.





SEs are intolerable Consult the Project Director.


Continuation and Maintenance Phase Treatment


Continuation Phase Treatment

1. Patient received pharmacotherapy during acute phase:

At baseline and throughout treatment, other psychosocial or nonmedication treatment modalities such asconcomitant psychotherapy should be considered. After full response, the medication(s) should becontinued for 6–9 months at the dose effective during the acute phase. Patients should be evaluated atleast once every 3 months during continuation treatment (preferably every 1–2 months). For initialepisodes of major depression, medication tapering and discontinuation should be considered after thecontinuation period is completed. If previous depressive episodes have occurred, maintenance treatmentshould be considered. When discontinuing the antidepressant, the dose should be tapered no morerapidly than 25% per week and not before 6–8 months of full remission has occurred. Tapering anddiscontinuation usually can be completed over a 2–3 month period. Patients should be educatedconcerning the signs and symptoms of recurrence of depressive symptoms. A new depressive episode ismost likely to occur within the first 8 months of medication discontinuation; therefore, patients should beevaluated every 2–4 months during that period. If depression recurs, prompt treatment with themedication previously effective should be initiated (i.e., initiate algorithm stage and tactic that previouslyresulted in remission of depressive symptoms).

No systematic studies regarding the optimal duration of antipsychotic treatment during the continuationphase have been reported. It is recommended that the acute phase antipsychotic at the same dose bemaintained at least for 1–2 months and then slowly tapered over the continuation phase. The duration ofantipsychotic treatment should be limited to the minimum duration indicated in order to reduce the risk oftardive dyskinesia. If a patient is receiving a TCA, the serum concentration should be monitored, and thedose adjusted as necessary to maintain the level with the recommended therapeutic window (with andwithout the neuroleptic co-administered).

2. Patient received ECT during acute phase:

Continuation treatment with an antidepressant is recommended. It is preferable to select anantidepressant that the patient has not received or one that the patient has responded to during aprevious episode of depression. However, if necessary, a previously ineffective antidepressant may beused in combination with lithium. Dosing, duration of treatment, monitoring, and medication tapering areas above.

If a patient relapses during continuation treatment with an antidepressant, continuation ECT should beconsidered.


Maintenance Phase Treatment

Patients experiencing an initial episode of major depression have at least a 50% chance of having asecond episode, and by the third episode of major depression, there is a 90% chance of recurrence.Therefore, all patients having a third depressive episode and some patients experiencing a secondepisode should be evaluated for maintenance antidepressant treatment.

Indications for Maintenance Medication

Feature Strength of Indication1. Three or more episodes of major depression Very strongly

recommended2. Two episodes of major depressive disorder, and one or

more of the following:a) Family history of bipolar disorder Strongly recommendedb) History of recurrence within one year after

previously effective medication was discontinuedStrongly recommended

c) A family history of recurrent major depression Strongly recommendedd) Early onset (before age 20) of the first depressive

episodeStrongly recommended

e) Depressive episodes were severe, sudden, or life-threatening within the past 3 years

Strongly recommended

(Source: AHCPR Guidelines (1993), Vol. 2, page 111.)

Maintenance medication should be continued at full therapeutic doses and, as in the continuation phase,the regimen associated with symptom remission is recommended. The optimal duration of maintenancetreatment has not been established, but depending on risk factors, is generally between one year pastcontinuation phase and lifetime administration.Active discussions regarding the initiation and duration of maintenance treatment are an importantelement in the clinician-patient collaboration for this as well as other phases of pharmacologicalmanagement of major depressive disorder. The patient's personal preference, as well as the risk factorsfor recurrence, should be considered in the decision process.


Appendix: Table of Contents DSM-IV Criteria for Major Depressive Disorder

Medication InformationAntidepressant MedicationsAugmentation AgentsAntipsychotic MedicationsSwitching Between Antidepressant MedicationsCombining Antidepressants

Process MeasuresInventory of Depressive Symptoms Self-Report (IDS-SR)Scoring Criteria for IDS-SRScoring Criteria for Physician- and Patient-Rated Overall Symptom and Side Effect Ratings

DocumentationInstructions for Outpatient Data Collection

Outpatient Intake FormOutpatient Clinic Visit Clinical Record FormOutpatient Interim Contact Form

Forms for Outpatient Data CollectionOutpatient Intake FormOutpatient Clinic Visit Clinical Record FormOutpatient Interim Contact Form

Instructions for Inpatient Data CollectionInpatient Intake Form/Annual UpdateInpatient Clinical Record FormInpatient Contact Form

Forms for Inpatient Data CollectionInpatient Intake Form/Annual UpdateInpatient Clinical Record FormInpatient Contact Form

CommunicationsImportant Telephone NumbersConference Call Schedule

Question and Response Fax Form


DSM-IV Criteria for Major Depressive DisorderCriteria for Major Depressive Episode

A. Five (or more) of the following symptoms have been present during the same 2-week period andrepresent a change from previous functioning: at least one of the symptoms is either (1) depressedmood or (2) loss of interest or pleasure.

Note: Do not include symptoms that are clearly due to a general medical condition, or mood-incongruent delusions or hallucinations.

(1) depressed mood most of the day, nearly every day, as indicated by either subjective report(e.g., feels sad or empty) or observation made by others (e.g., appears tearful). Note: Inchildren and adolescents, can be irritable mood.

(2) markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearlyevery day (as indicated by either subjective account or observation made by others)

(3) significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of bodyweight in a month), or decrease or increase in appetite nearly every day. Note: In children,consider failure to make expected weight gains.

(4) insomnia or hypersomnia nearly every day(5) psychomotor agitation or retardation nearly every day (observable by others, not merely

subjective feelings of restlessness or being slowed down)(6) fatigue or loss of energy nearly every day(7) feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly

every day (not merely self-reproach or guilt about being sick)(8) diminished ability to think or concentrate, or indecisiveness, nearly every day (either by

subjective account or as observed by others)(9) recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific

plan, or a suicide attempt or a specific plan for committing suicide

B. Symptoms do not meet criteria for a Mixed Episode.

C. The symptoms cause clinically significant distress or impairment in social, occupational, or otherimportant areas of functioning.

D. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse,a medication) or a general medical condition (e.g., hypothyroidism).

E. The symptoms are not better accounted for by Bereavement, i.e., after the loss of a loved one, thesymptoms persist for longer than 2 months or are characterized by marked functional impairment,morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotorretardation.


Diagnostic criteria for 296.2x Major Depressive Disorder, Single Episode

A. Presence of a single Major Depressive Episode.

B. The Major Depressive Episode is not better accounted for by Schizoaffective Disorder and is notsuperimposed on Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or PsychoticDisorder Not Otherwise Specified.

C. There has never been a Manic Episode, A Mixed Episode, or a Hypomanic Episode. Note: Thisexclusion does not apply if all of the manic-like, mixed-like, or hypomanic-like episodes aresubstance or treatment induced or are due to the direct physiological effects of a general medicalcondition.

Specify (for current or most recent episode):Severity/Psychotic/Remission SpecifiersChronicWith Catatonic FeaturesWith Melancholic FeaturesWith Atypical FeaturesWith Postpartum Onset

Diagnostic criteria for 296.3x Major Depressive Disorder, Recurrent

A. Presence of two or more Major Depressive Episodes.

Note: To be considered separate episodes, there must be an interval of at least 2 consecutivemonths in which criteria are not met for a Major Depressive Episode.

B. The Major Depressive Episodes are not better accounted for by Schizoaffective Disorder and arenot superimposed on Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or PsychoticDisorder Not Otherwise Specified.

C. There has never been a Manic Episode, a Mixed Episode, or a Hypomanic Episode. Note: Thisexclusion does not apply if all of the manic-like, mixed-like, or hypomanic-like episodes aresubstance or treatment induced or are due to the direct physiological effects of a general medicalcondition.

Specify (for current or most recent episode)Severity/Psychotic/Remission SpecifiersChronicWith Catatonic FeaturesWith Melancholic FeaturesWith Atypical FeaturesWith Postpartum Onset

Specify:Longitudinal Course Specifiers (With and Without Interepisode Recovery)With Seasonal Pattern


Antidepressant Monographs

Amitriptyline: Tricyclic antidepressant which blocks reuptake of norepinephrine and serotonin, into nerveendings. Peak plasma concentrations are reached within 2–12 hours. It is 90-97% protein bound andthus may cause drug interactions by displacing other agents from protein-binding sites. Amitriptyline andits metabolites are metabolized via multiple pathways, however amitriptyline is metabolized by the livervia cyt P450 2C9/19, with a half-life 10–50 hours. It does not alter hepatic metabolism. Contraindicated inthe recovery phase of myocardial infarctions, seizure disorders and prostatic hypertrophy. Increasesvasopressor effects of epinephrine and CNS depressant effects of alcohol, barbiturates, andbenzodiazepines. Possible hyperpyretic crisis, convulsions or hypertensive episode may occur if usedwith MAOIs; a 2-week washout is recommended before switching between TCA’s and MAOI’s.

Amoxapine: Tetracyclic antidepressant which blocks the reuptake of norepinephrine primarily, andserotonin weakly, into nerve endings. Its 7-hydroxy metabolite blocks dopamine receptors with potencycomparable to that of haloperidol. Peak plasma concentrations are reached within 1-2 hours. It is 90%protein bound. It is metabolized by the liver, with a half-life of 8-30 hours, and does not alter hepaticmetabolism. Contraindicated in the recovery phase of myocardial infarctions, convulsive disorders andprostatic hypertrophy. Increases vasopressor effects of epinephrine and CNS depressant effects ofalcohol, barbiturates, and benzodiazepines. Possible hyperpyretic crisis, convulsions or hypertensiveepisode may occur if used with MAOIs; a 2-week washout is recommended before switching betweenTCA’s and MAOI’s.

Bupropion (immediate release)/bupropion SR: an antidepressant which inhibits the reuptake ofdopamine and norepinephrine, with little effect on serotonin. Uses include major depression and smokingcessation. Peak plasma concentrations are reached within 3 hours, its half-life is 10-21 hours, and steadystate is achieved in 1 week. It is not highly protein bound. Bupropion is metabolized through the liver viamultiple isoenzymes and may be a weak inhibitor of cyt P450 2D6 activity. It is contraindicated in patientswith seizure disorders or eating disorders. Use cautiously in patients with renal and hepatic disease,recent MI or cranial trauma, or any patient with factors that may increase the risk of seizures.

Citalopram: an SSRI which is an effective inhibitor of neuronal serotonin reuptake. Absorption is fast,almost complete, and unaffected by food. Bioavailability is 80%, time to peak is 2-4 hours, with a half-lifeof 33 hours. Citalopram is 80 % protein bound with a low potential for displacement interactions. It ishepatically metabolized via cyt P450 2C9/19 isoenzymes and possesses very weak inhibitory effects on1A2, 2C9, and 2D6. Should not be used with MAOIs because the combination may lead to serotoninsyndrome (altered mental status, restlessness, hyperreflexia, diaphoresis, tremor).

Clomipramine: Tricyclic antidepressant which potently inhibits serotonin reuptake and increasesdopamine metabolism. Uses include major depression, dysphoria, phobias, anxiety, agoraphobia andobsessive-compulsive disorder. Extensively bound to tissue and plasma proteins and thus may displaceother agents from protein-binding sites. Peak plasma concentrations are reached within 2-6 hours and thehalf-life is 21 hours for the parent compound and 36 hours for metabolites. It is hepatically metabolizedvia cyt P450 2C9/19 isoenzymes but does not alter hepatic metabolism. Contraindicated in the recoveryphase of myocardial infarctions, convulsive disorders and prostatic hypertrophy. Increases vasopressoreffects of epinephrine and CNS depressant effects of alcohol, barbiturates, and benzodiazepines.Possible hyperpyretic crisis, convulsions or hypertensive episode may occur if used with MAOIs.


Desipramine: Tricyclic antidepressant which blocks the reuptake of norepinephrine into nerve ending.Peak plasma concentration is reached within 3-6 hours and protein binding ranges from 73-92%. It ishepatically metabolized via cyt P450 2D6, with a half-life of 11-46 hours. It does not alter hepaticmetabolism, however. Contraindicated in the recovery phase of myocardial infarctions, convulsivedisorders and prostatic hypertrophy. Increases vasopressor effects of epinephrine, and CNS depressanteffects of alcohol, barbiturates, and benzodiazepines. Possible hyperpyretic crisis, convulsions orhypertensive episode may occur if used with MAOIs.

Fluoxetine: an SSRI which is an effective inhibitor of neuronal serotonin reuptake .Uses include majordepression, obsessive-compulsive disorder and bulimia nervosa. Peak plasma concentrations arereached within 4-8 hours. It is >90% protein bound and thus may displace other agents from protein-binding sites. It is hepatically metabolized by cyt P450 2C9/19 , with a half-life of 4-6 days and 4-16 daysfor its active metabolite, norfluoxetine. Fluoxetine is a potent cyt P450 2D6 inhibitor, and norfluoxetine is acyt P450 3A4 inhibitor. Fluoxetine may increase the half-life of diazepam, tricyclic antidepressants,nefazodone, and some antipsychotics. TCA plasma concentration monitoring is recommended when thiscombination is used. Should not be used with MAOIs.

Fluvoxamine:. an SSRI which is an effective inhibitor of neuronal serotonin reuptake.Time to peak ranges between 2 and 8 hours and is not highly protein bound. It is eliminated via cyt P4501A2, with an elimination half-life of 15-26 hours. Fluvoxamine is a potent inhibitor of cyt P450 1A2 and2C19. An increase in the half-life of TCA’s may occur, therefore, TCA plasma concentration monitoring isrecommended. Like other SSRI’s, fluvoxamine should not be combined with MAOIs. The current FDAindication is for the treatment of Obsessive/Compulsive Disorder. However, since it is an SSRI, it is usedinvestigationally for the treatment of depression.

Imipramine: Tricyclic antidepressant which blocks the reuptake of norepinephrine and serotonin intonerve endings. It reaches peak plasma concentrations in 1.5-3 hours and is highly protein bound. It ismetabolized via cyt P450 1A2, with a half-life of 6-34 hours. Imipramine does not alter hepaticmetabolism. Contraindicated in the recovery phase of myocardial infarctions, convulsive disorders andprostatic hypertrophy. Increases vasopressor effects of epinephrine and CNS depressant effects ofalcohol, barbiturates, and benzodiazepines. Possible hyperpyretic crisis, convulsions or hypertensiveepisode may occur if used with MAOIs. Do not break, crush or chew imipramine film-coated tablets.

Mirtazapine: An antidepressant which blocks presynaptic alpha 2 inhibitory receptors and postsynapticserotonin receptors, thereby enhancing noradrenergic and serotonergic activity. Peak plasma levels arereached within 2 hours, and plasma protein binding is low. Mirtazapine is likely metabolized by cyt P4502D6, 1A2 and 3A4 but does not alter hepatic metabolism itself. The presence of food in the stomach hasa minimal effect on both the rate and extent of absorption.

Nefazodone: An antidepressant which selectively inhibits serotonin reuptake in the brain. Peakconcentrations are reached in 1–2 hours and is not highly protein bound. Metabolized in the liver via cytP450 3A4 with an elimination half-life of 2–4 hours. It is a potent inhibitor of cyt P450 3A4, and thusincreases plasma concentrations of some benzodiazepines, quetiapine, carbamazepine, and cisapride.Increases the effect of CNS depressants. Possible hypertensive crisis when combined with MAOIs. Druguse and smoking can increase metabolism and decrease effects. Use cautiously in patients withcardiovascular disease or seizure disorder.

Nortriptyline: Tricyclic antidepressant which blocks the reuptake of norepinephrine and serotonin intonerve endings. Peak plasma concentration is reached in 3-12 hours, and it is highly protein bound. It ishepatically metabolized by primarily cyt P450 2D6, with a half-life of 16-88 hours. It does not alter hepaticmetabolism. Contraindicated in the recovery phase of myocardial infarctions, convulsive disorders andprostatic hypertrophy. Increases vasopressor effects of epinephrine and CNS depressant effects of


alcohol, barbiturates, and benzodiazepines. Possible hyperpyretic crisis, convulsions or hypertensiveepisode may occur if used with MAOIs.

Paroxetine:. an SSRI which is an effective inhibitor of neuronal serotonin reuptake Uses include majordepression, obsessive-compulsive disorder, panic disorder and social phobia. Peak plasmaconcentrations are achieved in 5-7 hours. Protein binding is 95%. Paroxetine is metabolized through theliver via cyt P450 2D6, with a half-life of 21 hours. It is a potent inhibitor of cyt P450 2D6 metabolism, thusit may increase plasma levels of TCAs and some antipsychotics. Like other SSRI’s, it should not be usedwith MAOIs.

Phenelzine: MAOI antidepressant which increases concentrations of endogenous epinephrine,norepinephrine, serotonin, and dopamine in storage sites in the central nervous system by inhibitingMAO. Contraindicated in hypertension, elderly, CHF, severe hepatic disease, pheochromocytoma, severerenal disease and severe cardiac disease

Sertraline:. an SSRI which is an effective inhibitor of neuronal serotonin reuptake Uses include majordepression, obsessive-compulsive disorder, panic disorder and posttraumatic stress disorder. Sertralineplasma concentrations peak in 5–9 hours reaching steady state in 1 week. Taking with food decreasesthe time required to reach peak plasma levels but does not affect total concentration of drug absorbed. Itis 99% plasma protein binding with a half-life of 27 hours. It is hepatically metabolized via cyt P4502C9/19 and also has the ability to inhibit 2C9/19 and 2D6 activity, particularly at higher doses. May causefatal reactions when used in combination with MAOIs.

Tranylcypromine: MAOI antidepressant which increases concentrations of endogenous epinephrine,norepinephrine, serotonin, and dopamine in storage sites in the central nervous system by inhibitingMAO. Contraindicated in hypertension, elderly, CHF, severe hepatic disease, pheochromocytoma, severerenal disease and severe cardiac disease.

Venlafaxine/venlafaxine XR: Potent inhibitor of neuronal serotonin and norepinephrine reuptake and aweak inhibitor of dopamine reuptake. Peak plasma concentration is reached within 2 hours and proteinbinding is minimal. Extensively hepatically metabolized primarily via cyt P450 2D6 to an active metabolitewith 87% of drug recovered in the urine. The half-life for regular release and extended release are 5hours and 48 hours, respectively. May cause hyperthermia, rigidity, rapid fluctuations of vital signs andmental status changes when used with MAOIs. Use cautiously in patients with mania, hypertension orseizure disorder.


Note: When using any antidepressant agent in a patient with a history of manic symptoms,caution should be taken to monitor for precipitation of a manic episode.

Table 1. Characteristics of Antidepressant-Induced Sexual Dysfunction

Antidepressant Type of Sexual Dysfunction�� Incidence��Venlafaxine Impaired ejaculation, delayed/absent orgasm 12%Paroxetine Impaired ejaculation, delayed/absent orgasm 13-28%

2-10%Fluvoxamine Impaired ejaculation, delayed/absent orgasm 2-8%Sertraline Impaired ejaculation, delayed/absent orgasm 14%Citalopram Impaired ejaculation, delayed/absent orgasm,

decreased libido 1-3%*Fluoxetine Impaired ejaculation, delayed/absent orgasm,

decreased libido, and erectile impairment 2-11%Mirtazapine Decreased libido 2-6%*Nefazodone Decreased libido 1%*Bupropion Decreased libido 1-3%*MAOI’s Impaired ejaculation, delayed/absent orgasm,

erectile impairment, decreased libido NAΘ

TCA’s Impaired ejaculation, delayed/absent orgasm,erectile impairment, decreased libido NAΘ

�� Based on AHFS Drug Information and Hirschfeld RM, J Clin Psychiatry 1999;60(suppl 14):27-30Rothschild AJ, J Clin Psychiatry 2000;61(suppl 11):28-36.Montego-Gonzalez AL, et al. Journal of Sex & Marital Therapy 1997;23(3):176-94.

* No different than placeboΘ Case reports available

Note: Higher incidences of sexual dysfunction have been reported in settings where patients are specifically queried aboutsexual problems.


Monographs for Augmentation Agents

Lithium: Antimanic which may alter sodium, potassium ion transport across cell membrane in nerve cellsand may balance noradrenergic and serotonergic activity in the CNS by acting on postsynaptic secondmessengers. Peak plasma concentration is reached in 1-12 hours with no protein binding. It does notundergo hepatic metabolism but rather is eliminated renally. Half-life is 14-30 hours. Therapeutic rangeis 0.5-1.2 mEq/L. When adjusting dose, 300 mg of lithium will generally increase lithium serum levels by0.2-0.4 mEq/L. Sodium restriction, renal impairment, dehydration, vomiting/diarrhea, or other factors thatmay alter sodium levels or renal function may cause lithium toxicity. Contraindicated in hepatic disease,renal disease, brain trauma, and severe cardiac disease.

Buspirone: Antianxiety agent which acts by regulating the action of serotonin. May be used asaugmentation therapy due to increased effects when used with psychotropic drugs. Peak plasmaconcentration is reached within 1 hour. It is 95% protein bound, with a half-life of 2-3 hours. It ishepatically metabolized via cyt P450 3A4. Use cautiously in elderly patients and patients with impairedhepatic/renal functioning. Increased ALT when combined with trazodone. Do not use with MAOIs.

Liothyronine (T3): Increases metabolic rates, cardiac output, oxygen consumption, body temperature,blood volume, growth, and development at the cellular level. Peak plasma concentration is reached within2 hours, with a half-life of 1.5 days. Use cautiously in elderly patients and patients with angina pectoris,hypertension, ischemia, cardiac disease, pregnancy, and lactation. Increases the effects of TCAs, as wellas anticoagulants and sympathomimetics. Decreases the effects of digitalis drugs, insulin,hypoglycemics, liothyronine, and estrogens.

Antipsychotic Monographs

Haloperidol: A high potency traditional antipsychotic which blocks dopamine (D2) receptors at themesolimbic and mesocortical areas of the brain, thus treating psychotic symptoms. Peak plasmaconcentration is achieved within 3 hours and protein binding is low. Haloperidol is hepaticallymetabolized via cyt P4501A2 and 3A4, with a half-life of 15-30 hours. Contraindicated in alcohol andbarbiturate withdrawal states, Parkinson’s disease, angina, epilepsy, and urinary retention. Possibletoxicity when combined with epinephrine.

Olanzapine: An atypical antipsychotic which may mediate antipsychotic activity by both dopamine andserotonin type 2 antagonism. Peak plasma levels are reached within 5 hours. It is hepaticallymetabolized via cyt P450 1A2 and 2D6, with a half-life of 27 hours. Use cautiously in patients withhypertension, hepatic disease, cardiac disease and in elderly patients. Patients on olanzapine should bemonitored for weight gain, glucose intolerance and hyperlipidemia.

Perphenazine: A medium potency traditional antipsychotic which blocks dopamine (D2) receptors at themesolimbic and mesocortical areas of the brain, thus treating psychotic symptoms. Peak plasma level isachieved in 3-5 hours and protein binding is low. It is hepatically metabolized, with a half-life of 10-20hours.

Quetiapine: Neuroleptic antipsychotic which functions as an antagonist at dopaminergic and serotonergicreceptors in the brain. It has a higher affinity for serotonergic receptors than dopamine receptors. Peakplasma level is achieved in 1-2 hours, and protein binding is considered low (83%). Quetiapine is


hepatically metabolized by cyt P450 3A4 and possibly 2D6, with a half-life of 6 hours. It should be usedwith caution in patients taking antihypertensives and CNS depressants, and baseline liver function testsand thyroid panel should be obtained.

Risperidone: Neuroleptic antipsychotic which may mediate antipsychotic activity through both dopaminetype 2 and serotonin type 2 antagonism. Peak plasma concentration is reached in 1-2 hours, and proteinbinding is 90%. Risperidone is metabolized by cyt P450 2D6 to an active metabolite, 9-hydroxy-risperidone. The active metabolite is then eliminated renally. Half-lives for the parent compound andactive metabolite are 3 and 24 hours, respectively. Contraindicated in seizure disorders.

Note for all antipsychotic medications: Once psychotic symptoms have remitted, maintain thepatient on the lowest necessary dose to maintain remission for a period of 3 months. After 3months of no psychotic symptoms, gradually taper the patient off the antipsychotic medicationover a period of 2 weeks.

Table 2. Antidepressant/Antipsychotic Interactions

SUBSTRATE(Drug metabolized by pathway)INHIBITOR

(Inhibits substrate) 1A2 2D6 3A3/4Bupropion(Wellbutrin)

Phenothiazines (some)Clozapine*Olanzapine*

Citalopram(Celexa)

PhenothiazinesClozapine*Olanzapine*

Fluoxetine (Prozac)

PHENOTHIAZINESClozapine*Olanzapine*

ClozapineQuetiapine

Fluvoxamine (Luvox)

CLOZAPINEHALOPERIDOLOLANZAPINE

ClozapineQuetiapine

Nefazodone (Serzone)

CLOZAPINEQUETIAPINE

Paroxetine (Paxil)

PHENOTHIAZINESClozapine*Olanzapine*

Sertraline (Zoloft)

PhenothiazinesClozapine*Olanzapine*

ClozapineQuetiapine

Venlafaxine (Effexor) increases haloperidol levels, but not by Cytochrome P450 interaction.Regular type = small changes in levels (low probability of clinically significant interaction)Bold type = moderate changes in levels (moderate probability of clinically significant interaction)BOLD CAPS = very large changes in levels (high probability of clinically significant interaction)* = minor pathway


Monographs for other agents used to manage associated symptoms ortreatment emergent side effects

Amantadine: a antiparkinsonian agent that exerts its therapeutic effect by enhancing dopaminergicactivity, primarily through dopamine reuptake blockade. Peak plasma concentration is achieved in 1-4hours, and protein binding is low. The elimination half-life ranges between 10 and 31 hours, and it isprimarily excreted unchanged by the kidneys. Therefore, lower doses are recommended in patients withcompromised renal function. Because amantadine causes increases in dopamine levels initially, patientsmay experience visual hallucinations or symptoms of delirium. Symptoms will usually subside withcontinued treatment, however the lowest effective dose should always be used. In addition, to minimizethis effect, amantadine should not be combined with anticholinergic agents.

Alprazolam: a short-acting benzodiazepine that is FDA approved for the treatment of GAD. It exerts itsanxiolytic effect by enhancing GABA inhibition. Peak plasma level is reached in 1 hour, and proteinbinding is considered low (<90%). It is hepatically metabolized via cyt P450 3A4, and its half-life is 12-15hours. It has no active metabolites, and thus drug accumulation with chronic use is minimal. As with anybenzodiazepine, CNS depressant effects may be increased if combined with agents that have CNSdepressant properties (alcohol, barbiturates, narcotic analgesics, etc.). Tapering (25% reduction weekly)rather than abrupt discontinuation is recommended if a patient has been receiving benzodiazepinetherapy for at least 6 weeks. Withdrawal symptoms to monitor for include increased anxiety, insomnia,restlessness, and agitation/irritability.

Benztropine: an antimuscarinic, antiparkinsonian agent that acts to block acetylcholine and possiblyenhance dopaminergic activity, thus correcting the proposed dopamine deficiency-cholinergic excesstheory of pseudoparkinsonism. Peak plasma level is reached in and its half-life is > 24 hours. Tominimize sedation from its antihistaminic activity, bedtime administration is suggested.

Clonazepam: a benzodiazepine that is FDA approved for the treatment of seizures and panic disorder,but has clinical utility in the management of anxiety, drug-induced akathisia, catatonia and depression. Itacts by enhancing GABA activity. Peak plasma level is reached within 1-4 hours and protein binding is85%. Clonazepam is metabolized via cyt P450 3A4, with no active metabolites, and has an eliminationhalf-life of 30-40 hours. Its CNS depressant effects may be increased if combined with other agents thathave CNS depressant properties. If discontinuation is necessary, tapering (25% reduction weekly) isrecommended for patients taking clonazepam chronically for at least 6 weeks. Withdrawal symptoms tomonitor for include increased anxiety, insomnia, restlessness, and agitation/irritability. Clonazepam iscontraindicated in acute narrow angle glaucoma and significant liver disease.

Dextroamphetamine: a stimulant that is FDA approved for the treatment of ADHD and narcolepsy, buthas been tried clinically for the management of depression and obesity. Peak plasma levels are reachedwithin 1-2.5 hours, with a half-life of 10-12 hours. Adverse effects include nervousness, insomnia,anorexia, tachycardia, and changes in blood pressure. Most adverse effects can be resolved by loweringthe dose. As with other stimulants, it is contraindicated in arteriosclerosis, moderate/severe hypertension,hyperthyroidism, glaucoma, diabetes mellitus, agitated states, patients with a history of drugabuse/dependence and those on a monoamine oxidase inhibitor.

Lorazepam: a short-acting benzodiazepine that is FDA approved for the treatment of GAD. It exerts itsanxiolytic effect by enhancing GABA inhibition. Peak plasma level is reached within 2-4 hours. Protein


binding is considered low (< 90%). Lorazepam undergoes conjugation only and thus is not at risk forhepatic cyt P450 drug interactions. Lorazepam has no active metabolites and therefore drugaccumulation with repeated use is minimal. As with any benzodiazepine, CNS depressant effects may beincreased if combined with agents that have CNS depressant properties (alcohol, barbiturates, narcoticanalgesics, etc.). Tapering (25% reduction weekly) rather than abrupt discontinuation is recommended ifa patient has been receiving benzodiazepine therapy for at least 6 weeks. Withdrawal symptoms tomonitor for include increased anxiety, insomnia, restlessness, and agitation/irritability.

Methylphenidate: a stimulant that is FDA approved for the treatment of ADHD and narcolepsy, but hasbeen tried clinically for alleviation of antidepressant-induced sexual dysfunction, in doses of 5-25 mgtaken either daily or 1 hour before intercourse, and as augmentation therapy in depression, in doses of 5-30 mg daily. It is proposed that dopamine agonist activity may be responsible for its clinical benefits insexual dysfunction. Adverse effects include nervousness, insomnia, anorexia, tachycardia, and changesin blood pressure. Most adverse effects can be resolved by lowering the dose. Should be used withcaution in patients with hypertension, seizures or EEG abnormalities. It is contraindicated in glaucoma,Tourette’s Disorder, severe hypertension, hyperthyroidism, arteriosclerosis, patients with a history of drugabuse/dependence, persons with severe anxiety or agitation, and those on a monoamine oxidaseinhibitor.

Propranolol: a beta-adrenergic receptor blocker that is FDA approved as an antihypertensive agent, butis clinically used for the management of moderate anxiety and agitation in doses of 10-30 mg daily. Peakplasma level is reached within 1-1.5 hours and protein binding is high. Propranolol is hepaticallymetabolized via cyt P450 1A2, 2D6, 2C19 and has a half-life of 3-5 hours. Primary adverse effectsinclude bradycardia, dizziness, nausea/vomiting, fatigue and constipation. Should be used with caution inpatients with CHF, coronary artery disease, sinus node dysfunction, chronic bronchitis or emphysema. Itis contraindicated in patients with Raynaud’s syndrome, asthma, and 2nd or 3rd degree heart block.

Trazodone: an antidepressant that is chemically unrelated to TCA’s and SSRI antidepressants. ItInhibits serotonin reuptake and decreases adrenergic sensitivity. Trazodone is also highly sedating(antihistaminic effects) and therefore is clinically used to alleviate insomnia, in doses of 25-100 mg, 30-60minutes before bedtime. Peak plasma level is reached within 2 hours and protein binding ranges from85-95%. It is hepatically metabolized by cyt P450 2D6 and has a half-life of 7-8 hours. Primary adverseeffects are sedation, orthostatic hypotension, tachycardia, dry mouth, constipation, and blurred vision.

Zolpidem: a nonbenzodiazepine sedative-hypnotic that acts to enhance GABA inhibitory activity . Peakplasma level is reached within 0.5 hours and protein binding is high (92%). It is hepatically metabolizedby cyt P450 3A4 and has a half-life of 2 hours. Unlike benzodiazepines, zolpidem has minimal effect onsleep architecture, and the development of tolerance/physical dependence is rare. In doses of 5-10 mgnightly, no significant amnestic effect is observed.


Table 3. Fetal Effects of Psychotropic Agents

Medication 1st

Trimester2nd

Trimester3rd

Trimester Category* Summary

Tricyclicantidepressants

± + + D Possible association between 1st trimester and limbmalformation by some case reports but furtherstudies showed no association. Perinatalsyndromes: antidepressant withdrawal with jitterinessand irritability

SerotoninSelective Agents

± + + C Fluoxetine has been the most studied. No higherrates of major congenital malformation those whotook fluoxetine in the 1st trimester than the generalpopulation.

OtherAntidepressants

± + + C

Lithium ∅ + ± D Associated with cardiac anomalies when used in 1st

trimester.Prematurity associated with use in 2nd & 3rd trimester.Watch for maternal lithium toxicity after deliver due tovolume change-need to decrease dose by half beforedelivery.Lithium levels may be increased in neonates-risk of“floppy baby” & hypothyroidism

Valproic acid ∅ ∅ ∅ D Associated with neural tube defects/1-5% risk ofspina bifida

Carbamazepine ± ± ± C 0.5-1% risk of spina bifidaTypicalantipsychoticsHaloperidolChlorpromazineFluphenazineLoxapineMesoridazineThioridazineThiothixene

± ± ± C Most common malformations reported includecardiac, genital, skeletal (3.5%).Use of high potency agents is recommended.Avoid low potency agents due to decrease BP &uteroplacental blood flow.Use in 3rd trimester associated with neonatalassociated extrapyramidal effects such as agitation,tremor, poor sucking, swallowing, primitive reflexes,and hypertonicity/DC drugs 5-10 days prior todelivery to allow fetal drug level to decrease.

AtypicalantipsychoticsClozapine

± ± ± CB

Little information on atypical antipsychotics.

AnticholingericsBentropineTrihexiphenidylDiphenhydramine

±±±+

±±+

CCB

Main association is suggested cardiovascular effects.Possible association with minor malformationsBenadryl is the preferred agent

Propranolol ± + ± C It has been used to treat pregnancy inducedhypertension and does not appear to be associatedwith malformations. Neonatal adverse effects haveincluded hyperbilirubinemia, bradycardia, respiratorydepression, and low birth weights.

Benzodiazepines ∅ ± ± D Increase risk of cleft palate in 1st trimester, especiallydiazepam & alprazolam. 3rd trimester exposure leadsto tremors, hypertonicity, failure to feed, cyanosisand apnea. Best avoided but if needed uselorazepam (prn only).

Buspirone ± ± ± B Little information is available* Based on Drugs in Pregnancy and Lactation, 5th edition ∅ Use is not recommended+ May be used -least risk ± May be used if no other alternative available


Guidelines for Switching Between Antidepressant Medications

Switching From an SSRI

1. SSRI/#1 to SSRI/#2:• discontinue SSRI/#1 and then start SSRI/#2-or-• decrease SSRI/#1 to initiate SSRI/#2 to taper and discontinue SSRI/#1

Case Example: If patient. is on 40 mg po qam of fluoxetine: a) stop the fluoxetine and start paroxetine (orsertraline) the next day; or b) decrease the fluoxetine to 20 mg per day and add in paroxetine 20 mg (orsertraline 50 mg) per day for 1–3 days and discontinue the fluoxetine.

2. SSRI to TCA or bupropion:• discontinue SSRI and then start TCA or bupropion-or-• decrease SSRI to initiate TCA or bupropion at low dose to taper and discontinue SSRI, while

gradually increasing TCA or bupropion as tolerated to therapeutic dose range.*

* Both the TCAs and bupropion are associated with significant toxicity at elevated plasma concentrations.Since SSRIs increase the plasma concentrations of TCAs and bupropion (paroxetine > fluoxetine >sertraline > citalopram), caution is indicated when co-administering these agents or when therapy withbupropion or a TCA is undertaken in close proximity to cessation of an SSRI.

Case Example: If pt. is on 40 mg po qam of fluoxetine: a) stop the fluoxetine and start nortriptyline (orother TCA) or bupropion the next day; or b) decrease the fluoxetine to 20 mg po qam and add innortriptyline (25 mg po qhs or another TCA) or bupropion (50–75 mg po qd) for 1–3 days to discontinuefluoxetine and increase nortriptyline or bupropion as tolerated to therapeutic dose range.

3. SSRI to nefazodone or venlafaxine:• discontinue SSRI and then start nefazodone or venlafaxine-or-• decrease SSRI to initiate nefazodone (50–100 mg po qhs) or venlafaxine (37.5–75 mg po qd)

to taper and discontinue SSRI, while gradually increasing nefazodone or venlafaxine astolerated to therapeutic dose range.

Case Example: If patient is on 40 mg po qam of fluoxetine: a) stop the fluoxetine and start nefazodone(50–100 mg po qhs) or venlafaxine (37.5–75 mg po qd) the next day; or b) decrease the fluoxetine to 20mg po qam and add in nefazodone (50–100 mg po qhs) or venlafaxine (37.5–75 mg po qd) for 1–3 daysto discontinue fluoxetine and increase nefazodone and venlafaxine as tolerated to therapeutic doserange.

4. SSRI to MAOI:• discontinue SSRI and then after a 5 week washout period for fluoxetine or after a 2 week

washout period (sertraline or paroxetine), MAOI therapy can be safely initiated.


Switching from TCA, Venlafaxine, Nefazodone, or Bupropion

1. TCA/#1 (or venlafaxine, nefazodone, or bupropion) to TCA/#2:• discontinue TCA/#1 (or venlafaxine, nefazodone, or bupropion) by taper and then start TCA/#2-or-• decrease TCA/#1 (or venlafaxine, nefazodone, or bupropion) to initiate TCA/#2 to taper and

discontinue TCA/#1 (or venlafaxine, nefazodone, or bupropion), while gradually increasingTCA#2 as tolerated.

Case Example: If patient. is on 100 mg po qhs of nortriptyline (or venlafaxine, nefazodone, or bupropion):a) taper and then discontinue the nortriptyline (or venlafaxine, nefazodone, or bupropion) and start theother TCA the next day; or b) decrease the nortriptyline (or venlafaxine, nefazodone, or bupropion) andadd in doxepin (50–100 mg po qhs or other TCA) for 1–3 days and then taper and discontinue thenortriptyline (or venlafaxine, nefazodone, or bupropion).

2. TCA (or venlafaxine, nefazodone, or bupropion) to SSRI:• taper and discontinue TCA (or venlafaxine, nefazodone, or bupropion) and then start SSRI

-or-• decrease TCA (or venlafaxine, nefazodone, or bupropion) to initiate SSRI at low dose to taper

and discontinue TCA (or venlafaxine, nefazodone, or bupropion).

Case Example: If patient. is on nortriptyline (or venlafaxine, nefazodone, or bupropion): a) taper anddiscontinue the nortriptyline (or venlafaxine, nefazodone, or bupropion) and start fluoxetine (or otherSSRI) the next day; or b) decrease the nortriptyline (or venlafaxine, nefazodone, or bupropion) and add influoxetine (20 mg po qam or another SSRI) for 1–3 days to taper and discontinue nortriptyline (orvenlafaxine, nefazodone, or bupropion).

3. TCA (or venlafaxine, nefazodone, or bupropion) to nefazodone, venlafaxine, or bupropion:• discontinue TCA (or venlafaxine, nefazodone, or bupropion) and then start nefazodone,

venlafaxine, or bupropion-or-

• decrease TCA (venlafaxine, nefazodone, or bupropion) to initiate nefazodone (50–100 mg poqhs), venlafaxine (37.5–75 mg po qd), or bupropion (37.5–50 mg po qd) to taper anddiscontinue TCA (venlafaxine, nefazodone, or bupropion), while gradually increasingnefazodone, venlafaxine, or bupropion as tolerated to therapeutic dose range.

Case Example: If patient is on nortriptyline (or venlafaxine, nefazodone, or bupropion): a) stop thenortriptyline (or venlafaxine, nefazodone, or bupropion) and start nefazodone (50–100 mg po qhs),venlafaxine (37.5–75 mg po qd), or bupropion (37.5–50 mg po qd) the next day; or b) decrease thenortriptyline (or venlafaxine, nefazodone, or bupropion) and add in nefazodone (50–100 mg po qhs),venlafaxine (37.5–75 mg po qd), or bupropion (37.5–50 mg po qd) for 1–3 days to discontinuenortriptyline (or venlafaxine, nefazodone, or bupropion) and increase nefazodone, venlafaxine, orbupropion as tolerated to therapeutic dose range.

4. TCA to MAOI:• discontinue TCA and then after a 2 week washout period, MAOI therapy can be safely initiated.


Switching from an MAOI

1. MAOI/#1 to MAOI/#2, SSRI, TCA, venlafaxine, bupropion, nefazodone:• discontinue MAOI/#1 and then after a 2 week washout period, therapy with MAOI/#2 (or SSRI,

TCA, venlafaxine, or nefazodone) can be safely initiated.


Process Measures

Quick Inventory of Depressive Symptomatology (Self-Report) (QIDS-SR)

Scoring Criteria for QIDS-SR

Scoring Criteria for Physician- and Patient-Rated Overall Symptom and Side EffectRatings

The QIDS-SR consists of 16 individual items that the patient is asked to read and rate based upon his/herindividual perception of the presence and severity of common depression-related symptoms. If thepatient has difficulty reading or interpreting an item, it is appropriate for a staff member to read thequestion to the patient, but staff should not lead or influence the patient’s answer. Although somepatients may have difficulty using the form for the first time, most individuals should be able to easilycomplete it after the second or third time. Most patients also appreciate the opportunity to be able to tellthe physician and other staff about the symptoms that are bothering them. The QID-SR is constructed inorder to capture a range of DSM-IV related depressive symptoms in an individual patient, while at thesame time minimizing the tendency to over rate selected symptoms (e.g., sleep disturbance). For thisreason, the patient does not answer all of the questions. For example, on questions 6 and 7, addressingappetite disturbance, the patient only answers one of the questions (addressing either decreased orincreased appetite). If the patient has no appetite disturbance, they can answer either question. Thesame principles apply to questions 8 and 9. The QIDS-SR is also available in Spanish, and this versionshould be used for individuals who primarily read Spanish.

In scoring the QIDS-SR, the clinician does NOT sum all of the items to get the rating score. The scoringinstructions are listed on page two of the form. If the form is scored correctly, only 12 of the questions willbe summed to obtain the patient’s depression rating score, with a maximum possible score of 27. Thescoring criteria for the severity of depressive symptoms are listed below. Please note that these scoringcriteria are a guideline, and they should never be used as a substitute for the clinician’s judgementregarding the clinical status of the patient. Rather they are intended as a tool for the clinician to use inquantifying the severity of depressive symptoms and the response to treatment.


QIDS-SR Scoring Criteria

Normal ≤ 7

Mild 8 - 12

Moderate 13 - 16

Moderate to Severe 17 - 20

Severe 21 +


Scoring Criteria for Physician and PatientOverall Symptom and

Side Effect Ratings

0 = No Symptoms

1 = Borderline

2 = Mild

3 = Mild – Moderate

4 = Moderate

5 = Moderate – Marked

6 = Marked

7 = Marked – Severe

8 = Severe

9 = Severe – Extreme

10 = Extreme


Documentation

Instructions for Outpatient Data Collection

Outpatient Intake Form

The clinician documents the following identifying information on the intake form:

• Local Case #• MHMR Physician Code

(or first 4 digits of the physician’s Social Security number)

• Component/Clinic #• Date of Visit (i.e., date intake procedures initiated)

Note: Write in the month, day, year (e.g., 3/1/98)

• Age• Gender• Ethnic or Racial Group (check one only)

• Principal Diagnosis (i.e., DSM-IV Axis Code).(This diagnosis should coincide with the disease-specific module under consideration (i.e., majordepressive disorder, schizophrenia, or bipolar disorder).

• Age of Onset (pertains to principal diagnosis).

• Other Current DiagnosesNot including principal diagnosis (i.e., other comorbid Axis I conditions using the DSM-IV Axis I code).

• Alcohol/Substance Problem(Clinician rating within last six (6) months).

• Axis III(Record general medical conditions that the patient is currently receiving treatment for. Check all thatapply.)

• Note there is no need to document Axis IV.

• Family History of Mental IllnessCheck all that apply for each family member, indicating effective treatment in the last column.

• Number of Psychiatric Hospitalizations

• Psychoactive Medications Record past and current psychoactive medications taken in the last twoyears. Indicate the highest (daily) dose given for each.


Outpatient Clinic Visit Clinical Record FormThe following information is entered into the CRF by the clinician:



• Service Activity Code (Service activity or billing code for this visit.)

• Date of Visit (i.e., date intake procedures initiated)Note: Write in the month, day, year (e.g., 3/1/98)

• Duration:The difference between stop time and start time in minutes.

• Primary Current Dx:Please check the patient’s primary Axis I diagnosis for which the algorithm is being used.

• Stage in the AlgorithmRecord how many weeks the patient has been in this stage.

• Vital Signs• Most Recent Drug Levels• Prescription Medications

Check whether medications were or were not taken as prescribed.

• Other Medications Taken During Past Week(Not including medications prescribed by the physician.)

• Patient Global Self ReportRecord patient’s self-reported symptom and side effect severity on a scale of 0–10, “0” being noneand “10” being extreme.

• Clinical Rating ScalesRecord positive symptoms, negative symptoms, IDS-SR score, Altman score, and any others.

• Physician RatingsEach of the symptom clusters is rated on a 10-point scale (from “no symptoms” to “extremely severe”).The rating is based on your impression of the patient at this visit, as well as information you haveabout the patient’s clinical status during the week prior to the visit.

• Core Symptoms:Based upon all available information, clinician impression of the level of the presence of each ofthe symptoms in this patient.

• Other Symptoms:Clinician rating of other symptoms associated with the patient’s disorder, but not core symptoms ofthe patient’s illness. Rate your impression for each of the specific “other symptoms” listed(irritability, mood lability, insomnia, agitation, anxiety, level of interest, appetite, energy level).Under “other,” specify and rate any other symptom that you feel is significant.

• Overall Side Effect Severity:Overall rating of side effects from all medications being taken by the patient.


• Overall Functioning:Overall impression of this patient’s ability to function on a daily basis. “10” is the highest possiblefunctioning, and “1” is the lowest possible functioning.

• Prescription Information• Medication Name:

List the names of all psychotropic medications (for the core syndrome, other symptoms, or sideeffects) the patient is receiving — both new medications prescribed at this visit and continuingmedications. Check the appropriate box. If a medication is being discontinued, list the medicationname and check the D/C box.

List the complete SIG (dose and frequency) for each medication the patient is receiving. If amedication is being titrated or tapered, please outline the schedule. Indicate stop dates, ifapplicable. Please check whether the medication is for core syndrome (S), other symptoms (OS),or side effects (SE).

• Medication ResponseIndicate whether response to medication was full, partial, minimal, none, or the symptoms areworsening.

• Reason for Medication ChangeNote that this includes changing the dose for a current medication. Check all reasons that apply.

• Reasons for Medication ChoiceCheck reasoning for antidepressant, antipsychotic, mood stabilizer, and/or augmentation choice.

• Patient/Family EducationIndicate whether patient education was done at this visit and between last and current visit.

• Progress Note• Subjective

Patient report of sleep, appetite, side effects, medication efficacy, etc.

• ObjectivePhysician impression of patient’s orientation, appearance, rapport, speech patterns, suicidal orhomicidal ideations, psychosis, thought content and process, mood, affect, insight, judgement,cognition, etc.

• AssessmentsRecord diagnosis, clinical progress, formulations, problems, prognosis, and other appraisals.

• PlanCurrent direction for biopsychosocial treatment, discharge planning, placements, and other needs.

• Next visitIndicate how many weeks until patient should return to clinic, and what date the next appointment hasbeen set for.

• Physician Signature/Title

Outpatient Interim Contact FormIn the event that the patient does not come into the clinic or there is not time for a complete visit, the ICFis documented by support personnel or the physician.


• Case Number• Date of Patient Contact• Primary Diagnosis• Type of Contact

Indicate whether telephone or office visit.

• Prescription Medication in Last WeekRecord medication name, dosing and frequency information, and indicate whether medication wastaken as prescribed.

• Adherence to Medication TreatmentIndicate yes or no. If no, document in progress note.

• Significant Side Effects ReportedIndicate yes or no. If yes, describe side effects.

• Overall Patient Global ReportRecord symptom and side effect severity on a scale of 0–10.

• Suicidal/HomicidalIndicate yes or no.

• Progress NoteRecord any pertinent information regarding the patient’s clinical status (e.g., most prominentsymptoms, specific side effects, serum level results, psychosocial stressors, compliance, crisisinterventions, ER visits, information given to patient, etc.)

• Stage in the AlgorithmIndicate what stage, how many weeks in this stage, and whether a change to the current treatment isrecommended. If a treatment change is recommended, schedule a physician visit.

• Next Appointment Date• Signature/Title


Forms for Outpatient Data Collection

Outpatient Intake Form

Outpatient Clinic Visit Clinical Record Form

Outpatient Interim Contact Form

INTAKE OutpatientFinal Page 1 of 1

TIMA Texas Implementation of Medication Algorithms

Outpatient Intake FormDate of Visit: _____/_____/_____ MHMR Physician Code: _________________ mm dd yy

Age: ___ Gender: Female Ethnic or Racial Group (please check only one response): White Hispanic Male African-American Asian or Pacific Islander American Indian or Alaskan Native Other

Principal Diagnosis (DSM-IV Axis I code): ____ ____ ____ . ____ ____

Age at Onset: ______ # of Episodes: ______ Onset of Current Episode: _______________

Other current diagnoses not including principal diagnosis:Axis I: ____ ____ ____ . ____ ____ ____ ____ ____ . ____ ____ Axis II: ________________________

Alcohol/Substance Abuse: No Yes If yes, Current Past

Axis III (Current General medical conditions, check all that apply ): Hypertension Hypothyroidism Head Injury HIV CHF Diabetes Seizure Disorder Cancer Heart Disease Endocrine (Other) Stroke Chronic Lung Disorder Cardiac (Other) Asthma Neurological (Other) Allergies (If yes, explain below) Other Significant Systemic Illness (specify):______________________________

Additional Information:_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Any family members with a history of any of the following (please check all that apply):Depression Schizophrenia Bipolar Substance Abuse Suicide Other Effective Treatments

ParentSiblingChildrenAunt/UncleGrandparent

Number of Psychiatric Hospitalizations (best estimate): Past Year: ______ Past 5 Years: ______ Lifetime: ______

Past and Current Psychoactive Medications (Patient Self-Report/Records):

Signature/ title Date

MedicationPlease provide medications forthe past two years, record thehighest dose given

Taken forthis

episode?

Dose Freq. Start/Stop(Mo/Yr)

Response WellTolerated

1. Yes No Full Partial Minimal None Yes No









CRF OutpatientFinal Version Page 1 of 2

OutPatient Clinic VisitClinical Record Form

Date: ____/____/____ Service Activity Code: _______

Physician Code: __________ Start Time: _________ Stop Time: _______

Primary Current Dx: MDD-NP BPD-M BPD-D SCZ(check one) MDD-P BPD-MX SCZ-A (BP) SCZ-A Other (specify):

Stage: ______ Weeks in this stage: _______

Vital Signs: BP ______/______ Pulse ______ Temp ______ Weight ______ Height _______ (if needed)

Most Recent Drug Levels:Medication Name Date Drawn Serum Level WNL

Medications taken as Prescribed? Yes/Mostly No/Inadequate

Any other medications taken during the past week? No Yes (If yes, specify below) ______________________________________________________________________________________________________________________________________________________________________________________________________________________

Patient Global Self Report (0-10) 0 = No symptoms 5 =moderate 10 = extremeSymptom Severity: ____ Side Effects: _____

Clinical Rating ScalesPOS SX:____ NEG SX:____ IDS-SR:____ Altman:____ OTHER_____________________

Use for all physician’s ratings below: (0-10) 0 = No symptoms 5 =moderate 10 = extremeCore Symptoms: ____ Mania ____ Depression ____ Positive Sx or Psychoses ____ Negative Sx

Other Symptoms: ____ Irritability ____ Mood Lability ____ Insomnia ____ Agitation ____ Anxiety

Level of Interest Appetite Energy Level ____ Other (specify): ___________________________Overall Side Effect Severity: _____ (0-10)

Is patient presently suicidal? Yes No homicidal? Yes No Overall Functioning: _____ (0-10) If yes, comment in progress note. 0=Low 10=High

Prescription InformationMedication NameChange from previous visit?

No Yes

New/Continuing/Discontinue

Please provide information on titration, dose, dose frequency, duration themedication is to be taken, start and stop date (if applicable), and any otherpertinent information describing this medication.

Indication(check allthat apply)1

NewCont.D/C

S OS SE

NewCont.D/C

S OS SE

NewCont.D/C

S OS SE

NewCont.D/C

S OS SE

NewCont.D/C

S OS SE

1S=Meds Targeted at core syndrome. OS=Meds targeted at other symptoms. SE=Meds for side effects of S or OS

Are serum levels needed? Yes No (if yes, specify in progress note)


CRF OutpatientFinal Version Page 2 of 2

Medication Response: Full Partial Minimal None Symptoms Worsening

Reason for Medication Change (Include Dose Changes):

Critical Decision Point Indicates Change Necessary Insufficient Improvement Patient Preference

Side Effects Intolerable Symptoms Worsening Diagnosis Change Other: ______________________

Reason for Antidepressant Choice: SE Profile Pattern of Associated Sx Past Response Other: _________________

Reason for Antipsychotic Choice: SE Profile Pattern of Associated Sx Past Response Other: _________________

Reason for Mood Stabilizer Choice: SE Profile Pattern of Associated Sx Past Response Other: _________________

Reason for Augmentation Choice: SE Profile Pattern of Associated Sx Past Response Other: _______________ _

Patient/Family Education:Done at this visit? Yes No Between last visit and this visit? Yes No

Progress Note: ( Check here if note was dictated. Date of dictation _____/_____/_____)Subjective (Sleep, appetite, side effects, medication efficacy, other patient reports.)

Objective (Orientation, appearance, rapport, speech patterns, suicidal or homicidal ideations, psychosisthought content & process, mood, affect, insight, judgement, cognition, other observations)

Assessments (Diagnosis, clinical progress, formulations, problems, prognosis, other appraisals.)

Plan (Current direction for biopsychosocial treatment, discharge planning, placements, other needs.)

Return to clinic: ________ weeks Next appointment date: / /

Signature/Title:__________________________________________________________________________

ICF OutpatientFinal Page 1 of 1


Outpatient Interim Contact Form

Case #: ____________________________ Date: ______/_______/_______

Primary Diagnosis: MDD-NP BPD-M BPD-D SCZ (check one) MDD-P BPD-MX SCZ-A (BP) SCZ-A Other (specify):________________

Type of Contact: Telephone Office VisitAll Prescription Medications In Last WeekMedication Name – Please provide information on dosing, frequency and any other pertinentinformation.

Was themedication takenas prescribed?

1. YesNo

2. Yes No

3. Yes No

4. Yes No

5. Yes No

Adherence to medication treatment? Yes No If no, document in progress note.

Significant Side Effects Reported? Yes No If yes, describe: _______________________________________________________________________________________________________________________________________

Overall Patient Global (self report): 0=none 5=moderate 10=extremeSymptom Severity: (0-10)___________ Side Effects: (0-10) ____________

Is patient currently suicidal? Yes No homicidal? Yes No

Progress Note

Stage: _______ Weeks in Stage: _______ Change to Treatment Recommended? YES NO

IF yes, schedule physician visit. Appointment Date: _____/_____/_____

Signature/Title: ______________________________________________________________________

TIMA


Instructions for Inpatient Data CollectionInpatient Intake Form/Annual UpdateThe clinician documents the following identifying information on the intake form:

• Initial Visit or 90-Day Review (Check which applies.)

• Date of VisitNote: Write in the month, day, year (e.g., 3/1/98)



• Age• Gender• Ethnic or Racial Group (check one only)

• Principal Diagnosis (i.e., DSM-IV Axis Code).(This diagnosis should coincide with the disease-specific module under consideration (i.e.,major depressive disorder, schizophrenia, or bipolar disorder).

• Age of Onset (pertains to principal diagnosis).

• Number of Episodes• Onset of Current Episode• Other Current Diagnoses

Not including principal diagnosis (i.e., other comorbid Axis I conditions using the DSM-IVAxis I code).

• Alcohol/Substance Problem(Clinician rating within last six (6) months).

• Axis III(Record general medical conditions that the patient is currently receiving treatment for.Check all that apply.)Note there is no need to document Axis IV.

• Family History of Mental IllnessCheck all that apply for each family member, indicating effective treatment in the lastcolumn.

• Number of Psychiatric HospitalizationsBest estimate for the past year, past five years, and complete lifetime.

• Psychoactive MedicationsRecord past and current psychoactive medications taken in the last two years. Note which(if any) medications were taken for this episode. Indicate the highest (daily) dose given foreach, frequency, start/stop dates, response, and whether medication was tolerable.

TIMA


Inpatient Clinical Record FormThe following information is entered into the CRF by the clinician:

• Local Case #• Date of Visit (i.e., date intake procedures initiated)

Note: Write in the month, day, year (e.g., 3/1/98)

• Time of Day• TIMA Stage

Note what stage patient is in and the number of weeks in this stage.

• Physician Code• Type of Review

Indicate whether daily, weekly, monthly, quarterly, or other.

• Patient Seen and Chart ReviewedIndicate yes or no.

• Level of ServiceIndicate low, medium, or high.

• Primary Current Dx:Please check the patient’s primary Axis I diagnosis for which the algorithm is being used.

• Physician RatingsEach of the symptom clusters is rated on a 10-point scale (from “no symptoms” to“extremely severe”). The rating is based on your impression of the patient at this visit, aswell as information you have about the patient’s clinical status during the week prior to thevisit.

• Core Symptoms:Based upon all available information, clinician impression of the level of the presence ofeach of the symptoms in this patient.

• Other Symptoms:Clinician rating of other symptoms associated with the patient’s disorder, but not coresymptoms of the patient’s illness. Rate your impression for each of the specific “othersymptoms” listed (irritability, mood lability, insomnia, agitation, anxiety, level of interest,appetite, energy level). Under “other,” specify and rate any other symptom that you feelis significant.

• Psychotropic Medication Information• Medication Name:

List the names of all psychotropic medications (for the core syndrome, other symptoms,or side effects) the patient is receiving — both new medications prescribed at this visitand continuing medications. Check the appropriate box. If a medication is beingdiscontinued, list the medication name and check the D/C box.

List the complete SIG (dose and frequency) for each medication the patient is receiving.If a medication is being titrated or tapered, please outline the schedule. Indicate stop

TIMA


dates, if applicable. Please check whether the medication is for core syndrome (S),other symptoms (OS), or side effects (SE).

• Change from Medication AlgorithmIndicate yes or no. if yes, check all reasons for changing the medication that apply.

• Reasons for Medication ChoiceCheck reasoning for antidepressant, antipsychotic, mood stabilizer, and/or augmentationchoice.

• Patient Global Self ReportRecord patient’s self-reported symptom and side effect severity on a scale of 0–10, “0”being none and “10” being extreme.

• Clinical Rating ScalesRecord MMSE score, AIMS score, positive symptoms, negative symptoms, IDS-SR score,Altman score, and any others.

• Serum Levels NeededIndicate yes or no. Record medication name, the date that serum level was drawn, and theserum level.

• Labs WNLIndicate yes or no. If no, describe pertinent lab data.

• Patient/Family EducationIndicate whether patient education was done at this visit and between last and current visit.

• Progress Note• Subjective

Patient report of sleep, appetite, side effects, medication efficacy. Check all that apply,and note any pertinent comments.

• ObjectivePhysician impression of patient’s orientation, appearance, rapport, speech patterns,thought content and process, mood, affect, insight, judgement, cognition, psychomotoractivity, and memory. Check all that apply, and note any pertinent comments.

• AssessmentsNote whether psychiatric condition is generally improving, unchanged, or deteriorating.Record diagnosis, clinical progress, formulations, problems, prognosis, and otherappraisals.

• PlanCurrent direction for biopsychosocial treatment, discharge planning, placements, andother needs.

• Continuation of Psychiatric Hospital ServicesIndicate whether this is necessary because treatment can reasonably be expected toimprove the patient’s condition and/or for the purposes of Diagnostic Study.

• Physician Signature

INTAKE InpatientFinal Page 1


Inpatient Intake Form/Annual Update Initial Visit 90-day review Date: _____/_____/_____

MHMR Physician Code: _____________ Length of Contact: __________

Age: ___ Gender: Female Ethnic or Racial Group (please check only one response): White Hispanic Male African-American Asian or Pacific Islander American Indian or Alaskan Native Other

Principal Diagnosis (DSM-IV Axis I code): ____ ____ ____ . ____ ____

Age at Onset: ______ # of Episodes: ______ Onset of Current Episode: _____________

Other current diagnoses not including principal diagnosis:

Axis I: ____ ____ ____ . ____ ____ ____ ____ ____ . ____ ____ Axis II: ________________________

Alcohol/Substance Problem (within last 6 months): Yes No (If yes, specify substance): _______________________

Axis III (Current General medical conditions, check all that apply ): Hypertension Hypothyroidism Head Injury HIV CHF Diabetes Seizure Disorder Cancer Heart Disease Endocrine (Other) Stroke Chronic Lung Disorder Cardiac (Other) Asthma Neurological (Other) Allergies (If yes, explain below) Other Significant Systemic Illness (specify):______________________________

Additional Information:_____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Any family members with a history of any of the following (please check all that apply):Depression Schizophrenia Bipolar Substance Abuse Suicide Other Effective Treatments

ParentSiblingChildrenAunt/UncleGrandparent

Number of Psychiatric Hospitalizations (best estimate): Past Year: ______ Past 5 Years: ______ Lifetime: ______

Past and Current Psychoactive Medications (Patient Self-Report/Records): Please provide medications for the past two years, record the highestdose given.

Signature/ title Date

Medication Taken forthis

episode?

Dose Freq. Start/Stop(Mo/Yr)

Response WellTolerated










Inpatient CRF Final.docFinal Version Page 1 of 2

Clinical Inpatient Record Form

Date: ____/____/____ Time: _______

TIMA Stage: _______ Weeks in this stage: _______ Physician Code: __________

Type of Review : Daily Weekly Monthly Quarterly Other

Patient seen and chart reviewed? Yes No Level of Service Low Medium High

Primary Current Dx : MDD-NP BPD-M BPD-D SCZ Other (specify):

(check one) MDD-P BPD-MX SCZ-A (BP) SCZ-A

Use for all physician’s ratings below: (0-10) 0 = No symptoms 5 =moderate 10 = extremeCore Symptoms: ____ Mania ____ Depression ____ Positive Sx of Psychosis ____ Negative Sx of PsychosisOther Symptoms: ____ Irritability ____ Mood Lability ____ Insomnia ____ Agitation ____ Anxiety

____ Appetite Level of Interest Energy Level Other

Psychotropic Medication InformationMedication Name

Document any new or discontinuedmedications, or dosage changes of

established medications.

Dosing Information

Please provide information on titration, dose, dose frequency, duration themedication is to be taken, start and stop date (if applicable) and any other

pertinent information describing this medication.

Indication(Check all

thatapply.)1

NewChangeD/C

S OS SE

NewChangeD/C

S OS SE

NewChangeD/C

S OS SE

NewChangeD/C

S OS SE

NewChangeD/C

S OS SE

NewChangeD/C

S OS SE

S=Meds Targeted at core syndrome. OS=Meds targeted at other symptoms. SE=Meds for side effects of S or OS 1

Change from medication algorithm recommended? YES NO (If yes, check all that apply)

Patient previously failed next step. Next step not acceptable to patient. Next step not available at this site.

Next step not medically safe for this patient. No options left. Other _______________________________

Reason for Antidepressant Choice: SE Profile Pattern of Associated Sx Past Response Other: _________________

Reason for Antipsychotic Choice: SE Profile Pattern of Associated Sx Past Response Other: __________________

Reason for Mood Stabilizer Choice: SE Profile Pattern of Associated Sx Past Response Other: __________________

Reason for Augmentation Choice: SE Profile Pattern of Associated Sx Past Response Other: __________________

Patient Global Self Report (0-10) 0 = No symptoms 5 =moderate 10 = extremeSymptom Severity: ____ Side Effects: _____

Clinical Rating ScalesMMSE____ AIMS___ POS SX:____ NEG SX:____ IDS-SR:____ Altman:____ OTHER_____________________


Inpatient CRF Final.docFinal Version Page 2 of 2

Are serum levels needed? Yes No Labs WNL? Yes No If no, describe below.Medication Name Date Drawn Serum Level

Patient Education Completed? Yes No=========================================================================================== Progress Note ( Check here if note was dictated. Date of dictation _____/_____/_____)

Subjective (Sleep, appetite, side effects, medication efficacy, other patient reports.)

Objective (Orientation, appearance, rapport, speech patterns, suicidal or homicidal ideations, psychosisthought content & process, mood, affect, insight, judgement, cognition, other observations)

Assessments (Diagnosis, clinical progress, formulations, problems, prognosis, other appraisals.)

Plan (Current direction for biopsychosocial treatment, discharge planning, placements, other needs.)

Inpatient Psychiatric Hospital Services continues to be medically necessary for : Treatment which can reasonably be expected to improve the patient’s condition and/or Diagnostic Study

Physician Signature :

Pertinent Lab Data :


©2000, A. John Rush, M.D., University of Texas Southwestern Medical Center at Dallas

Communications

Important Phone Numbers

Madhukar H. Trivedi, M.D.UT Southwestern Medical CenterDepartment of Psychiatry5959 Harry Hines POB1 Suite 600Dallas, TX 75235-9101

Office number (214) 648-4282Fax number (214) 648-4210To be paged (214) 648-3300E-mail address: [email protected]

M. Lynn Crismon, Pharm. D.Clinical Pharmacy DivisionUT College of Pharmacy200 W. University Ave. (PHR 5.110)Austin, TX 78712-9101

Office number (512) 232-2630Fax Number (512) 471-3756Pager number (512) 397-7102TDMHMR number (512) 206-5068TDMHMR fax (512) 206-4744E-mail address: [email protected]

Conference Call Schedule

Teleconferences are designed to be a forum for discussion of the implementation of the algorithm.General and specific questions related to the algorithm may be asked during these time periods.Additionally, time may be spent addressing particular clinical or therapeutic issues. The length ofeach teleconference may vary depending on the type/number of questions, with a maximum time limitof 60 minutes. Please call the Office of the Medical Director (512/206-4511) for schedule information.



QUICK INVENTORY OF DEPRESSIVE SYMPTOMATOLOGY (SELF-REPORT)(QIDS-SR)

NAME: _________________________________________ TODAY’S DATE __________________

Please circle the one response to each item that best describes you for the past seven days.

1. Falling Asleep:

0 I never take longer than 30 minutes tofall asleep.

1 I take at least 30 minutes to fall asleep,less than half the time.

2 I take at least 30 minutes to fall asleep,more than half the time.

3 I take more than 60 minutes to fallasleep, more than half the time.

2. Sleep During the Night:

0 I do not wake up at night.1 I have a restless, light sleep with a few

brief awakenings each night.2 I wake up at least once a night, but I

go back to sleep easily.3 I awaken more than once a night and

stay awake for 20 minutes or more,more than half the time.

3. Waking Up Too Early:

0 Most of the time, I awaken no morethan 30 minutes before I need to getup.

1 More than half the time, I awaken morethan 30 minutes before I need to getup.

2 I almost always awaken at least onehour or so before I need to, but I goback to sleep eventually.

3 I awaken at least one hour before Ineed to, and can't go back to sleep.

4. Sleeping Too Much:

0 I sleep no longer than 7-8 hours/night,without napping during the day.

1 I sleep no longer than 10 hours in a24-hour period including naps.

2 I sleep no longer than 12 hours in a24-hour period including naps.

3 I sleep longer than 12 hours in a 24-hour period including naps.

5. Feeling Sad:

0 I do not feel sad1 I feel sad less than half the time.2 I feel sad more than half the time.3 I feel sad nearly all of the time.



Please complete either 6 or 7 (not both)

6. Decreased Appetite:

0 There is no change in my usualappetite.

1 I eat somewhat less often or lesseramounts of food than usual.

2 I eat much less than usual and onlywith personal effort.

3 I rarely eat within a 24-hour period, andonly with extreme personal effort orwhen others persuade me to eat.

7. Increased Appetite:

0 There is no change from my usualappetite.

1 I feel a need to eat more frequentlythan usual.

2 I regularly eat more often and/orgreater amounts of food than usual.

3 I feel driven to overeat both atmealtime and between meals.

Please complete either 8 or 9 (not both)

8. Decreased Weight (Within the Last TwoWeeks):

0 I have not had a change in my weight.1 I feel as if I've had a slight weight loss.2 I have lost 2 pounds or more.3 I have lost 5 pounds or more.

9. Increased Weight (Within the Last TwoWeeks):

0 I have not had a change in my weight.1 I feel as if I've had a slight weight gain.2 I have gained 2 pounds or more.3 I have gained 5 pounds or more.

10. Concentration/Decision Making:

0 There is no change in my usualcapacity to concentrate or makedecisions.

1 I occasionally feel indecisive or findthat my attention wanders.

2 Most of the time, I struggle to focus myattention or to make decisions.

3 I cannot concentrate well enough toread or cannot make even minordecisions.



11. View of Myself:

0 I see myself as equally worthwhile anddeserving as other people.

1 I am more self-blaming than usual.2 I largely believe that I cause problems

for others.3 I think almost constantly about major

and minor defects in myself.

12. Thoughts of Death or Suicide:

0 I do not think of suicide or death.1 I feel that life is empty or wonder if it's

worth living.2 I think of suicide or death several times

a week for several minutes.3 I think of suicide or death several times

a day in some detail, or I have madespecific plans for suicide or haveactually tried to take my life.

13. General Interest:

0 There is no change from usual in howinterested I am in other people oractivities.

1 I notice that I am less interested inpeople or activities.

2 I find I have interest in only one or twoof my formerly pursued activities.

3 I have virtually no interest in formerlypursued activities.

14. Energy Level:

0 There is no change in my usual level ofenergy.

1 I get tired more easily than usual.2 I have to make a big effort to start or

finish my usual daily activities (forexample, shopping, homework,cooking or going to work).

3 I really cannot carry out most of myusual daily activities because I justdon't have the energy.

15. Feeling slowed down:

0 I think, speak, and move at my usualrate of speed.

1 I find that my thinking is slowed downor my voice sounds dull or flat.

2 It takes me several seconds to respondto most questions and I'm sure mythinking is slowed.

3 I am often unable to respond toquestions without extreme effort.

16. Feeling restless:

0 I do not feel restless.1 I'm often fidgety, wringing my hands, or

need to shift how I am sitting.2 I have impulses to move about and am

quite restless.3 At times, I am unable to stay seated

and need to pace around.

TIMA

To Score:

1. Enter the highest score on any 1 ofthe 4 sleep items (1-4) ____

_2. Item 5 ____

_3. Enter the highest score on any 1

appetite/weight item (6-9)

_____

4. Item 10 _____

5. Item 11 _____

6. Item 12 _____

7. Item 13 _____

8. Item 14 _____

9. Enter the highest score on either ofthe 2 psychomotor items (15 and16)

_____

TOTAL SCORE (Range 0-27) _____

TIMA

©2000, A. John Rush, M. D., The University of Texas Southwestern Medical Center

EL INVENTARIO RÁPIDO DE SINTOMATOLOGÍA DE LA DEPRESIÓN (REPORTE PERSONAL)(QIDS-SR)

NOMBRE: _______________________ LA FECHA DE HOY:___________________________

Por favor marque la respuesta en cada sección que mejor describa los últimos siete días.

1. SUEÑO:

0 Nunca tomo más tiempo que 30 minutos para dormirme.1 Tomo al menos 30 minutos para dormirme, no me toma más de la mitad del tiempo.2 Tomo por lo menos 30 minutos para dormirme, esto me pasa la mayoría de las veces.3 Tomo más que 60 minutos para dormirme, esto me pasa la mayoría de las veces.

2. DORMIR DURANTE LA NOCHE:

0 No me despierto durante la noche.1 Tengo un sueño ligero inquieto, y a veces me despierto cada noche.2 Me despierto por lo menos una vez cada noche, pero vuelvo a dormirme fácilmente.3 Despierto más de una vez cada noche y me quedo despierto por 20 minutos o más, la mayoría de

las veces.

3. DESPERTARSE DEMASIADO TEMPRANO:

0 La mayoría del tiempo, despierto no más que por 30 minutos antes de que yo necesite levantarme.1 Más de la mitad del tiempo, despierto por más de 30 minutos antes de que yo necesite levantarme.2 Casi siempre me despierto por lo menos por una hora aproximadamente antes de que yo necesite

levantarme, pero me vuelvo a dormir al rato.3 Despierto por lo menos una hora antes de que yo necesite levantarme , y no puedo volver a dormir.

4. EL DORMIR DEMASIADO:

0 Duermo no más que 7-8 horas por noche, sin tomar una siesta durante el día.1 Duermo no más que 10 horas incluyendo siestas durante un período de 24 horas.2 Duermo no más que 12 horas incluyendo siestas durante un período 24 horas.3 Duermo más que 12 horas, incluyendo siestas durante un período de 24 horas.

5. EL SENTIRSE TRISTE:

0 No me siento triste.1 Me siento triste menos de la mitad del tiempo.2 Me siento triste más de la mitad del tiempo.3 Me siento triste casi todo el tiempo.

6. EL APETITO DISMINUIDO:

0 No hay cambio en mi apetito usual.1 Frecuentemente como algo menos ó en menor cantidades de alimento que lo usual.2 Como mucho menos que lo usual y solamente con esfuerzo personal.3 Como raramente durante un período de 24 horas, y solamente con esfuerzo personal extremo o

cuando otros me persuaden que coma.

TIMA


7. EL AUMENTO DE APETITO:

0 No hay cambio en mi apetito usual.1 Siento una necesidad de comer más frecuentemente que lo usual.2 Como regularmente más frecuentemente y/o mayores cantidades de alimento que lo usual.3 Me siento conducido a sobrealimentarme tanto en la hora de comer como entre comidas.

8. EL PESO DISMINUSIÓN (Durante las Dos Últimas Semanas):

0 No he tenido un cambio en mi peso.1 Siento como si he tenido una pérdida de peso ligera.2 He perdido 2 libras o más.3 He perdido 5 libras o más.

9. EL PESO AUMENTO (Durante las Dos Últimas Semanas):

0 No he tenido un cambio en mi peso.1 Siento como si he tenido una ganancia de peso ligera.2 He ganado 2 libras o más.3 He ganado 5 libras o más.

10. LA CONCENTRACIÓN Y EL HACER DECISIONES:

0 No hay cambio en mi usual capacidad de concentrarme o de hacer decisiones.1 Me siento ocasionalmente indeciso ó encuentro que mi atención es muy poca.2 La mayoria del tiempo, lucho por concentrar mi atención o para hacer decisiones.3 No puedo concentrarme bastante bien para leer o no puedo hacer hasta decisiones menores.

11. LO QUE PIENSO DE MI MISMO:

0 Me veo con tanto mérito e igualmente meritorio como la otra gente.1 Me culpo más que lo usual.2 Creo ampliamente que provoco problemas para otros.3 Pienso casi constantemente acerca de defectos mayores y menores en mi mismo.

12. LOS PENSAMIENTOS DE MUERTE O DE SUICIDIO:

0 No pienso en el suicidio o la muerte.1 Considero que la vida no tiene sentido y me pregunto se ésta vida tiene valor.2 Pienso en el suicidio o la muerte varias veces por semana por varios minutos.3 Pienso en el suicidio o la muerte varias veces al día con bastante detalle, ó he hecho planes

específicos para suicidarme ó he realmente intentado terminar mi vida.

13. INTERÉS GENERAL:

0 No hay cambio en general de la manera que me siento interesado en otros y en actividades.1 Noto que estoy menos interesado en la gente o en actividades.2 Encuentro que estoy interesado solamente en uno o dos actividades que anteriormente yo hacia.3 Tengo virtualmente no interés en actividades que yo anteriormente hacia.

TIMA


14. EL NIVEL DE ENERGÍA

0 No hay cambio en mi usual nivel de energía.1 Me canso más fácilmente que lo usual.2 Tengo que hacer un esfuerzo grande para comenzar ó acabar mis usuales actividades diarias (por

ejemplo, compras, tarea, cocinar o yendo a trabajar).3 Realmente no puedo llevar a cabo la mayoría de mis usuales actividades diarias porque

precisamente no tengo la energía.

15. SENTIRSE MAS LENTO QUE LO USUAL

0 Pienso, hablo, y me muevo tan rápido como antes.1 Encuentro que mi pensamiento es mas lento o mi voz suena sin ánimo y aburrida.2 Me toma varios segundos para responder a la mayoría de las preguntas y yo estoy seguro que mi

pensamiento está demasiado lento.3 Me siento frecuentemente incapaz de responder a las preguntas a menos que haga un esfuerzo

extremo.

16. SENTIRSE INQUIETO

0 No me siento inquieto.1 Estoy frecuentemente inquieto, escurro mis manos, o necesito cambiar donde estoy sentando.2 Tengo impulsos de estar moviéndome y me siento bastante inquieto.3 A veces me siento incapaz de permanecer sentado y necesito pasearme de un lado al otro.

To Score:

1. Enter the highest score on any 1 of the4 sleep items (1-4) _____

2. Item 5 _____3. Enter the highest score on any 1

appetite/weight item (6-9) _____4. Item 10 _____5. Item 11 _____6. Item 12 _____7. Item 13 _____8. Item 14 _____9. Enter the highest score on either of the

2 psychomotor items (15 and 16) _____

TOTAL SCORE (Range 0-27) _____

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